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This review is a summary of published studies that contain drug residue depletion data for edible tissues and milk following treatment of sheep and goats. The information is separated by antibiotic class for ease of comparison between studies. This summary is useful for understanding medication residue depletion following extra-label drug use and can be used to help estimate withdrawal intervals in order to help protect the human food chain.

Abstract

This review provides a summary of extracted data from the published literature that contains drug residue depletion data for edible tissues and milk following treatment of sheep and goats. Out of 20,234 records obtained during the initial search, data from 177 records were included in this review. The data is separated by antibiotic class for ease of comparison between studies. Extracted data includes the active ingredient, dosing information, animal health status, analytical method and limits of detection, tolerance and maximum residue limit information, and time frames relative to residue absence or detection. This information is useful for understanding drug residue depletion profiles following extra-label use and for estimating withdrawal intervals, in order to protect the human food chain.

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1. Introduction

Drinking water and availability of food for both humans and animals are affected by climate change that lowers rainfall and an increasing world population, especially in semi-arid climates [1]. Small ruminants present a unique opportunity for developing nations, specifically in developing nations that are in semi-arid climates, due to their multi-purpose use (meat, milk and fibers), lower production cost compared to large ruminants, and tolerance to low rainfall and hot climates [1].

According to data from the Food and Agriculture Organization of the United Nations (FAO), the number of sheep and goats worldwide has increased from approximately 1.4 billion head combined (1 billion sheep, ~400 million goats) in 1961 to approximately 2.3 billion head combined (~1.2 billion sheep, ~1.1 billion goats) in 2019 [2]. Between 2014 and 2019, the largest producers of sheep meat worldwide were China, Australia, New Zealand, Turkey and Algeria, whereas during this same time period, the largest producers of goat meat worldwide were China, India, Pakistan, Nigeria and Bangladesh.

In the United States, sheep and goats are considered minor species by the Food and Drug Administration (FDA) [3]; however, sheep are considered major species while goats are considered minor species by the European Medicines Agency (EMA) Committee for Medicinal Products for Veterinary Use [4]. In the United States, there is a “severe shortage of approved new animal drugs for use in minor species” [5].

The Food Animal Residue Avoidance and Depletion Program (FARAD) is a United States Department of Agriculture (USDA)-funded program with a mission to provide veterinary practitioners with scientifically based withdrawal interval recommendations following extra-label drug use or chemical/pesticide contamination in food-producing species. FARAD call submission data for small ruminants indicates a steady increase in the number of withdrawal interval request submissions from 2015 to 2019, with a steep increase in the number of submissions in 2020 (2015 = 435 submissions for sheep, 223 for goats; 2019 = 343 submissions for sheep, 710 for goats; 2020 = 595 submissions for sheep, 1401 for goats). The most commonly requested drug categories include antibiotics, anthelmintics, and non-steroidal anti-inflammatory drugs (NSAIDs). This data reflects the increasing numbers of backyard or hobby-farm environments, where the food-products are consumed by the family keeping the sheep or goats. Given the limited FDA-approved medications for use in sheep or goats, drugs are commonly prescribed in an extra-label manner which is legalized by the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) [6].

Given the importance of sheep and goats as commodity groups worldwide, the purpose of this review is to summarize research studies investigating antibiotic medication use in small ruminants with respect to the potential for drug residues to be present in small ruminant meat and milk products. Due to the large volume of published literature in small ruminants, this review only includes antibacterial medications; however, a second review will be completed incorporating anthelmintics and other medication classes not included here. It is important to note that residue depletion times referenced in the text are based on data from scientific studies. Normal industry practice to withdraw feed 8 to 12 h prior to processing the animals in order to minimize fecal contamination [7] may not have occurred in scientific research studies examining a zero day withdrawal. In addition, the residue depletion times listed in this manuscript are dependent on the sensitivity of the analytical method utilized in the study. Summaries of drug residue studies, drug approvals, tolerances (in the United States), and maximum residue limits (MRLs; in the European Union) have been provided in the tables for the reader’s convenience. If available, FDA-approved medications for use in sheep and goats should be utilized according to directions and labeled withdrawal times adhered to in order to guarantee human food safety.

2. Materials and Methods

2.1. Search Strategy

A systematic literature search was conducted using various databases and compared to publications included FARAD Program’s literature database. The aim of the search was to collect milk and edible tissue residue data for antibiotics that had been administered to small ruminants. Published literature between 1926 and 2021 was searched using PubMed, Cab Direct, Scopus, and Web of Science. Search terms and key words included: “sheep”, “goat(s)”, “small ruminants”, “caprine”, “ovine”, “drug absorption”, “clearance”, “drug residue(s)”, “pharmacokinetics”, “metabolic clearance rate”, “intestinal absorption”, “bioavailability”, “biological availability”, “metabolism”.

2.2. Screening Results

For systematic screening, search results were imported into the Covidence online platform (Covidence Systematic Review Software, Veritas Health Innovation, Melbourne, Australia) and duplicate results were removed by the Covidence software. Initially, the 20,234 “Titles and Abstracts” were screened by one reviewer (EDR or CED) for relevancy and categorized as ‘yes’, ‘no’, or ‘maybe’ using predetermined inclusion and exclusion criteria. The category of ‘maybe’ was used for trials that did not explicitly state the inclusion or exclusion criteria in the abstract and thus required further review of the full text. Inclusion criteria were as follows: in vivo sheep or goat drug trial; drug or metabolite concentration data and time point in tissue and/or milk; drug dose, route of administration, and dosing frequency stated. Exclusion criteria were as follows: any animal not a sheep or goat; in vitro study; concentration or residue data for non-drug substances (pesticide, toxin, vitamins) or drugs of abuse; drug plasma or serum concentrations only; dose of drug, route of administration, and dosing frequency missing. After initial screening for exclusion criteria, 1769 ‘yes’ and ‘maybe’ results moved to a ‘Full Text’ screening by one reviewer (EDR, KLM, or CED). These records were further excluded or included based on the above criteria and a reason was assigned. Records were excluded due to: not being a study (e.g., review, short communication, corrigendum; n = 128), not being able to verify text (e.g., full text not available from lenders worldwide, abstract only from proceedings, text unable to be translated; n = 141), being the wrong patient population/study design (e.g., not in live animals, in live animals other than small ruminants, etc.; n = 84), chemical product of study was a non-drug substance (n = 10), matrices under study did not consist of tissues or milk (n = 1076), and lack of specific concentration versus time presented in the paper (n = 60). A total of 270 records met the complete inclusion criteria. Figure 1 displays a flowchart representation of the screening process completed in this literature search.

For comparison, the FARAD database returned 832 records for both sheep and goats; however, 78 records were removed from the review due to incorrect matrices (i.e., plasma or serum data only). Ultimately, only 177 records met the complete inclusion criteria.

3. Data Extraction and Presentation (Antibiotic Drug Classes, Residue Detection, and Analytical Methods)

The published literature presenting tissue and milk residue data for antibiotics used in sheep and goats is presented in the Tables below and is categorized by antibiotic class. Tolerances or maximum residue limits are presented for FDA-approvals and EMA-approvals, respectively. The basic analytical method is described, with a focus on the limit of detection and limit of quantitation, alongside the dosing regimen for each study. Animal health status and additional information are also included, since variations in health- or lactation-status may affect drug residue depletion. Finally, two columns are included to indicate when residues were last detected. The column titled ‘Last sampling time point for which residues WERE detected (post-last treatment)’ refers the last sampling point when residues were detected based on the study sampling protocol. This is in contrast to the column titled ‘Sampling time point when NO residues were detected (post-last treatment)’ which refers to the last sampling point when residues were not detected based on the study sampling protocol. Instances where a greater than symbol (“>”) is utilized refers to situations where residues were still detected at the last sampling time point of the study protocol.

Data for the summarized studies includes analytical methods since it is important to consider how those methods impact the sensitivity of drug residue detection and how the analytical limits of detection compare to tolerances or MRLs. Newer analytical methods can detect drug residues at lower concentrations than historical microbiological bioassays or colorimetric testing, resulting in a greater number of days with detectable drug residues. In contrast, studies using less sensitive methods, having higher limits of detection, may have found shorter periods with detectable drug residues upon withdrawal of the drug. Readers are cautioned to keep the sensitivity of the analytical methods in mind when evaluating the data presented within this review, as well as the fact that most of the studies were completed in healthy animals. It is also important to note that US products approved for use in small ruminants should be used according to the FDA-approved label directions. The FDA-approved label withdrawal time should take precedent above any of the data summarized in this paper.

When considering antibiotic drug classes, it is important to remember that the World Health Organization (WHO) classifies antibiotics into categories based on their place in therapy for some infections in human medicine. These categories include critically important, highly important and important [8]. Some critically important antibiotics are then sub-divided by priority if they are considered sole or limited therapy for some infections in human medicine [8]. Some cephalosporins (third, fourth and fifth generations), quinolones, macrolides are classified as highest priority critically important antibiotics for human health. Aminoglycosides, some cephalosporins (first and second generations) are classified as high priority critically important antibiotics. Amphenicols, some penicillins (antipseudomonal, aminopenicillins with and without beta-lactamase inhibitors, amidinopenicillins, anti-staphylococcal, narrow spectrum), sulfonamides and tetracyclines are classified as highly important antibiotics for human health by the WHO.

3.1. Aminoglycosides

Aminoglycosides (amikacin, apramycin, dihydrostreptomycin, gentamicin, tobramycin, neomycin, streptomycin) are concentration dependent, bactericidal antibiotic agents produced from Streptomyces spp. and Micromonospora spp. Aminoglycosides act by irreversibly binding to the 30s subunit of the bacterial ribosome thereby inhibiting protein synthesis. Their spectrum of activity includes mostly Gram-negative bacteria, with some mycobacteria and staphylococci coverage. Transmission of Enterococcus spp., Enterobacteriaceae (including E. coli), and Mycobacterium spp. can occur from non-human sources and potentially result in human infection. Therefore, the appropriate use of aminoglycosides in food animal species is essential to maintain human safety.

Aminoglycosides are generally not well absorbed from the gastrointestinal tract [9], unless there is damage to the intestinal mucosa. When administered parenterally, aminoglycosides are rapidly and completely absorbed. Elimination of aminoglycosides is primarily renally, which may result in persistent residues in the kidneys. In most published studies in sheep and goats, residues in renal tissue exceeded the duration of the study [10,11,12,13,14,15,16,17]. In humans, aminoglycosides are poorly excreted into breastmilk [18]. This may also be the case for sheep and goats as a few studies have shown short duration of residue detection in milk following IV and IM administration [19,20,21,22,23,24,25,26].

In the United States, the only aminoglycoside FDA-approved for use in small ruminants is neomycin sulfate. However, the EMA has approved streptomycin/dihydrostreptomycin and kanamycin for sheep, while also extending MRLs from other species for gentamicin and neomycin. Table 1 shows the published literature that provides data for edible tissue or milk residues of aminoglycosides following treatment of sheep and goats.

3.2. Amphenicols

Amphenicols (chloramphenicol, florfenicol, thiamphenicol) are broad-spectrum antibiotics. These antibiotics are typically bacteriostatic agents that act by inhibiting microbial protein synthesis by binding to the 50s bacterial ribosomal subunit. Amphenicols are broad-spectrum against many aerobic and anaerobic Gram-positive and Gram-negative bacteria.

Little pharmacokinetic data is available following the use of amphenicols in sheep or goats. The limited data available in goats shows that florfenicol and thiamphenicol residues do enter the milk after intramuscular and intravenous administration, however tissue data was not available [35,36]. In one study, thiamphenicol concentrations were higher in the mammary gland that was frequently stripped compared to the gland that was not [35].

In the United States, there are no amphenicol products FDA-approved for use in sheep or goats. Chloramphenicol is prohibited from use in food producing animals in several countries including the United States, European Union, and Canada [6,37,38] due to the risk of blood dyscrasias, such as aplastic anemia and bone marrow suppression, in humans. Table 2 summarizes the published literature evaluating edible tissue or milk residues of amphenicols following treatment of sheep and goats.

3.3. Penicillin and Penicillin-Derivatives

Penicillins (penicillin G procaine, penicillin G benzathine) and penicillin-derivatives (amoxicillin, ampicillin, cloxacillin, dicloxacillin, nafcillin) are bactericidal antibiotics that act by inhibiting cell wall synthesis. These antibiotics display a broad spectrum of activity against many Gram-positive and Gram-negative bacteria, including anaerobic bacteria.

Amoxicillin and ampicillin show limited milk penetration or accumulation, even when the blood-milk barrier is altered in cases of mastitis [47,48]. However, beta-lactam products labeled for intramammary administration in cattle can result in very high antibiotic concentrations within the small ruminant udder due to the differences in both body and udder size [49,50]. Consequently, intramammary administration of cattle-labeled products to small ruminants can lead to persistent residues present in the milk and require extended withdrawal intervals beyond the labeled withdrawal times for cattle [49,51,52,53,54].In the United States, penicillin G procaine is FDA-approved for use in sheep via intramuscular administration. In the EU, MRLs have been extended from bovine species to all ruminants for nafcillin.

Due to the potential for allergic reactions to penicillin and penicillin-derivatives in humans, caution must be exhibited to ensure food-products from small ruminants do not contain traces of penicillins [55,56]. Table 3 summarizes the published literature evaluating edible tissue or milk residues of beta-lactams or penicillins following treatment of sheep and goats.

3.4. Cephalosporins

Cephalosporins (first-generation: cephapirin, cefacetrile, cephalothin, cephradine, cephalexin; second-generation: cefonicid; third-generation: ceftazidime, ceftiofur, ceftriaxone; fourth-generation: cefquinome, cefepime) are beta-lactam antibiotics divided into five ‘generations’ based on the spectrum of activity (first-generation cephalosporins are active against Gram-positive bacteria but not Gram-negative bacteria, while each consecutive generation has increased activity against Gram-negative bacteria with decreased Gram-positive activity). In the United States, cephalosporins are permitted to be used in an extra-label manner in minor species, such as sheep and goats, unlike major food producing species (cattle, swine, chickens & turkeys).

In general, cephalosporins have low penetration into milk [62,63,64,65,66] with variable pharmacokinetic parameters and slower milk depletion in mastitic animals [67,68]. Cephalexin exhibited a nearly double terminal serum elimination half-life in ewes compared to cattle, in addition to increased concentrations of cephalexin residues [69]. Cephapirin exhibited a longer presence of residues in goat samples compared to cattle when used for mastitis treatment [70].

Ceftiofur sodium (Naxcel®) is currently the only FDA-approved cephalosporin for use in sheep and goats with a 0 day meat and milk withdrawal time. Pharmacokinetic parameters of both intravenous and intramuscular ceftiofur sodium are found to be similar between sheep and goats when administered at the same dose [71]. Table 4 summarizes the published literature evaluating edible tissue or milk residues of cephalosporins following treatment of sheep and goats.

3.5. Fluoroquinolones/Quinolones

Fluoroquinolones (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, levofloxacin, marbofloxacin, moxifloxacin, norfloxacin, orbifloxacin, pefloxacin, sarafloxacin) are broad-spectrum antibiotics that exhibit concentration-dependent bactericidal activity via inhibition of DNA gyrase in bacterial cells. As a drug class, fluoroquinolones exhibit a high lipid solubility, low protein binding, high bioavailability (especially after parenteral administration) and large volumes of distribution in most species, including small ruminants [81,82,83,84,85,86,87,88,89,90,91,92,93,94,95]. Due to the importance of fluoroquinolones to human health, fluoroquinolones are prohibited from extra-label drug use in food-producing species in the United States.

Studies suggest that the pharmacokinetics of fluoroquinolones change during lactation due to the increased elimination of the drug from serum [88,96]. Additionally, multiple fluoroquinolones extensively penetrate into milk, with some drugs in the class exhibiting up to a 10× higher concentration in milk compared to plasma or serum [88,96,97,98]. This variation can be useful in mastitis cases since these drugs can accumulate in the milk at concentrations above the MIC for a sustained period of time [96,97,99].

In the United States, there are no fluoroquinolones FDA-approved for use in small ruminants, and due to the stipulations outlined by AMDUCA in the CFR, fluoroquinolones are prohibited from extra-label use in food-producing species [6]. In the European Union, flumequine is the only approved fluoroquinolone for use in sheep, while MRLs have been extended from bovine species to all food-producing species for enrofloxacin. Table 5 summarizes the published literature evaluating edible tissue or milk residues of quinolones following treatment of sheep and goats.

3.6. Macrolides

Marcolides (erythromycin, gamithromycin, spiramycin, tilmicosin, tulathromycin and tylosin) are a group of bacteriostatic compounds that bind to the 50S bacterial ribosomal subunit inhibiting bacterial protein synthesis and cell growth [110]. These antibiotics are effective against Mycoplasma spp. and Gram-positive organisms, and less effective against Gram-negative organisms.

Penetration into tissues, milk and blood are shown to be relatively quick with high systemic availability [111]. Macrolides show good penetration and distribution into the udder. In particular, tilmicosin and tulathromycin have been shown to have persistent drug residues in the milk [112,113,114,115,116,117], thus they are not recommended for use in lactating animals. Erythromycin, spiramycin and tylosin also exhibit good udder penetration, but result in shorter withdrawal intervals [29,60,111,118,119,120,121,122]. Some small ruminant macrolide pharmacokinetic parameters (absorption, volume of distribution and elimination) were found to be similar to those reported in cattle [111,112,116,123,124].

In the United States, the only FDA-approved macrolide for use in sheep is tilmicosin; however, this approval specifically excludes lactating sheep. Therefore, no tolerance has been established for milk. In the European Union, multiple macrolides are approved for use in small ruminants: gamithromycin and tilmicosin in sheep, and tulathromycin in both sheep and goats. Additionally, MRLs have been extended from other species for erythromycin, tilmicosin (in goats) and tylosin. Table 6 summarizes the published literature evaluating edible tissue or milk residues of macrolides following treatment of sheep and goats.

3.7. Sulfonamides

Sulfonamides (sulfadiazine, sulfadimethoxine, sulfamethoxazole, sulfachlorpyrazine) are bacteriostatic antibacterial medications that complete with para-aminobenzoic acid disrupting folic acid synthesis. They are active against Gram-positive and Gram-negative bacteria and protozoa.

One study administered sulfonamides in both normal and mastitic ewes. Sulfonamide concentrations were found to be much higher in the mastitic ewe milk, which the authors attributed in part to the increase in milk pH of mastitic milk [131]. Another study found that some sulfonamides are found in the milk in higher concentrations than blood, whereas others (sulfathiazole, sulfadimidine, sulfadiazine and sulfacetamide) are found in the milk in lower concentrations than blood [132].

Due to the potential for allergic reactions to sulfonamides, caution must be exhibited to ensure food-products from small ruminants do not contain traces of sulfonamides [133,134]. In the US, extra-label use of sulfonamides is prohibited in dairy cattle 20 months of age and older, due to allergic potential of affected milk and increased violative residues.

In the United States, there are no sulfonamide products FDA-approved for use in small ruminants, whereas there are some sulfonamide active ingredients with established milk MRLs for small ruminants in the EU. Table 7 summarizes the published literature evaluating edible tissue or milk residues of sulfonamides following treatment of sheep and goats.

3.8. Tetracyclines

Tetracyclines (chlortetracycline, doxycycline oxytetracycline, tetracycline) are broad-spectrum antibiotics that act by inhibiting the 30S bacterial ribosomal subunit thus inhibiting protein synthesis. They are active against Gram-positive and Gram-negative bacteria, as well as some atypical mycobacteria and protozoa [144,145,146].

In oxytetracycline- and chlortetracycline-treated animals, milk production decreased 15% [147]. Infusion of drug into one half of the udder resulted in diffusion of low concentrations into the untreated udder half [147].

Following intramammary infusion of chlortetracycline, residues were detected for a shorter time in goat milk compared to cow milk; however, parenteral chlortetracycline administration results in similar milk residue depletion between goats and cows [122].

In the United States, there are multiple tetracycline approvals for both sheep and goats: chlortetracycline (medicated feed for sheep), oxytetracycline (sheep) and tetracycline (sheep and goats; only topical administration for goats). In the EU, MRLs have been determined for chlortetracycline, oxytetracycline and tetracycline in all food-producing species. Table 8 summarizes the published literature evaluating edible tissue or milk residues of tetracyclines following treatment of sheep and goats.

4. Conclusions

The judicious use of medications and drug residue avoidance is an important topic in animal agriculture and for veterinarians treating animals that provide food for humans. Although there are numerous published studies that describe drug residues in sheep and goat meat and milk, they are scattered throughout the primary literature. In this review, these studies are compiled, and data extracted for easy reference to help facilitate a comprehensive overview of the scientific data, with respect to drug residues in edible tissues and milk from sheep and goats for antibiotics used in small ruminant practice.

Author Contributions

Conceptualization, L.A.T.; methodology, L.A.T.; visualization, M.O.C.; writing—original draft preparation, E.D.R. and L.A.T.; writing—review and editing, K.L.M. and C.E.D.; project administration, L.A.T. All authors have read and agreed to the published version of the manuscript.

 Institutional Review Board Statement

Not applicable.

 Informed Consent Statement

Not applicable.

 Data Availability Statement

The original contributions presented in this review are included in the main manuscript and included tables. Further inquiries can be directed to the corresponding author.

 Conflicts of Interest

The authors declare no conflict of interest.

 Abbreviations
AMDUCA Animal Medicinal Drug Use Clarification Act of 1994
CFR Code of Federal Regulations
EMA European Medicines Agency
FAO Food and Agriculture Organization of the United Nations
FARAD Food Animal Residue Avoidance and Depletion Program
FDA Food and Drug Administration
MIC Minimum inhibitory concentration
MRL Maximum residue limit
NSAIDs Non-steroidal anti-inflammatory drugs
USDA United States Department of Agriculture
WHO World Health Organization

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figure and Tables
View Image - Figure 1. Schematic diagram of the process for three independent evaluators to assess published manuscripts and the numerical outcome of each step. The ultimate goal was to curate manuscripts with tissue and milk residue data from live sheep and goat antibacterial drug studies.

Figure 1. Schematic diagram of the process for three independent evaluators to assess published manuscripts and the numerical outcome of each step. The ultimate goal was to curate manuscripts with tissue and milk residue data from live sheep and goat antibacterial drug studies.

Aminoglycoside residues in milk or edible tissue samples from sheep or goats following treatment.

Analyte Species; Breed; Age; # of Animals per Time Point Tolerance/ MRL Analytical Method LOD LOQ Route of Admin-istration Dose & Active Ingredient # of Doses Matrix Last Sampling Time Point (Post-Last Treatment) When Residues WERE Detected Sampling Time Point When NO Residues Were Detected (Post-Last Treatment) * Health Status Additional Information Source/Year
Amikacin Goat; Baladi; 2–3 years; n = 5 US Tol: Not established. EMA MRL: Not established. Bioassay NS 0.2 ppm IV 7.5 mg/kg Amikacin sulfate 1 Milk 4 h (0.22 ppm) 6 h Healthy Mid- lactation; Milked 2× [19] 1999
IM 7.5 mg/kg Amikacin sulfate 1 Milk 6 h (0.21 ppm) 8 h
Amikacin Goat; NS; 1.5–2 years; n = 6 US Tol: Not established. EMA MRL: Not established. Bioassay 0.1 ppm NS IM 10 mg/kg Amikacin sulfate 1 Milk 5 h (NS) 6 h Healthy Lactating [20] 2001
Amikacin Sheep; crossbred; 2–4 years; n = 6 US Tol: Not established. EMA MRL: Not established Bioassay NS 0.19 ppm IV 7.5 mg/kg Amikacin sulfate 1 Milk 9.5 h (0.85 ppm §) >1 day Healthy Lactating; Milked 2×/day [21] 2004
IM 7.5 mg/kg Amikacin sulfate 1 Milk 9.5 h (0.21 ppm §) >1 day
Apramycin Goat; Saanen; adult; n = 10 US Tol: Not established. EMA MRL: Not established. Bioassay NS 0.1 ppm IV 20 mg/kg Apramycin sulfate 1 Milk 10 h (0.12 ppm §) >10 h Healthy Early Lactation [22] 1995
Apramycin Sheep; Awassi; adult; n = 6 US Tol: Not established. EMA MRL: Not established. Bioassay NS 0.1 ppm IM 10 mg/kg Apramycin sulfate 1 Milk 720 min (0.15 ppm §) 1440 min Diseased-Mastitis Mid-lactation [22] 1995
Apramycin Sheep; Awassi; adult; n = 10 US Tol: Not established. EMA MRL: Not established. Bioassay NS 0.1 ppm IV 20 mg/kg Apramycin sulfate 1 Milk 6 h (0.11 ppm §) 8 h Healthy Mid-lactation [22] 1995
Apramycin Sheep; NS; Lambs; n = 12 study; n = 3/time pt US Tol: Not established. EMA MRL: Not established. Bioassay 500 ppb NS PO 10 mg/kg Apramycin daily 3 Liver ND@1 day 1 day Healthy NS [10] 1999
Kidney 21 days (1730 ppb) 35 days
Muscle ND@1 day 1 day
Fat 21 days (960 ppb) 28 days
NS; Lambs; n = 20 study; n = 4/time pt HPLC Liver: 368 ppb Liver: 2500 ppb PO 10 mg/kg Apramycin daily 5 Liver 30 days (700 ppb) >30 days
Kidney: 394 ppb Kidney: 2500 ppb Kidney 30 days (1700 ppb) >30 days
Muscle: 124 ppb Muscle: 500 ppb Muscle ND @ 6 days 6 days
Fat: 42 ppb Fat: 500 ppb Fat ND @ 6 days 6 days
Apramycin Goat; NS; Adult; NS US Tol: Not established. EMA MRL: Not established. NS NS NS IM 20 mg/kg Apramycin 1 Milk 10 h (NS) 12 h NS NS [23] 2000
IV 20 mg/kg Apramycin 1 Milk 12 h (NS) >12 h
Dihydro- strepto-mycin Goat; NS; Adults; n = 220 US Tol: Not established. EMA MRL: Not established. Bioassay 0.13 ppm 0.15 ppm IMM 300,000 IU Procaine benzyl-penicillin; 100 mg dihydro-strepto-mycin; 100 mg nafcillin 1 Milk 6 days post kidding (≥0.2 ppm) 7 days post kidding Healthy Dry off period (mean 61.0 ± 4.3 days SD (range 23–156 days); 1 tube per gland before drying off. Sample collected after kidding [27] 1995
Dihydro-strepto-mycin Sheep; Lacaune; adult; n = 8 US Tol: Not established. EMA established MRL: 200 ppb (milk). Bioassay 0.02 ppm NS IMM 300,000 IU Procaine benzyl-penicillin; 100 mg dihydro-streptomycin; 100 mg nafcillin 1 Milk 3 days (0.02 ppm §) 4 days Healthy Dry off period (mean 112 days (range 85–223 days); 1 tube per gland before drying off. Sample collected after lambing [28] 1995
Dihydro-strepto-mycin Sheep; Awassi; adult; n = 3 US Tol: Not established. EMA established MRL: 200 ppb (milk). Bioassay NS NS IV 20 mg/kg Dihydro-streptomycin (radio-labeled) then 10 mg/kg for 4 doses 45 min interval 5 Milk 24 h (0.20 ppm §) 36 h Healthy Lactating; Milked 2×/day [24] 1973
Radio-activity NS NS IV 5 Milk 8 h (1.83 ppm §) 10 h
Dihydro-strepto-mycin Sheep; NS; NS; n = 22 study n = 4/time pt US Tol: Not established. EMA established MRL: 500 ppb (liver, muscle, fat); 1000 ppb (kidney). Bioassay 0.5 ppm NS IM 10 mg/kg Dihydro-streptomycin combined w/ 10,000 IU procaine penicillin-G daily 5 Kidney 28 days (0.8 ppm) >28 days Healthy NS [11] 1995
Muscle 14 days (0.07 ppm) 21 days
Inj. Site 28 days (0.2 ppm) >28 days
Dihydro-strepto-mycin Sheep; Awassi; Adult; n = 2 US Tol: Not established. EMA established MRL: 200 ppb (milk). Bioassay NS NS IM 20 mg/kg Dihydro-streptomycin (radio-labeled) 1 Milk 12 h (0.22 ppm §) 24 h Healthy Lactating [29] 1974
Milk 48 h (0.11 ppm §) 56 h Disease-mastitis
Radio-activity NS NS IM Milk 48 h (0.75 ppm §) >48 h Healthy
Milk 12 h (0.42 ppm §) 24 h Disease-mastitis
Dihydro-strepto-mycin Sheep; NS; NS; n = 12 study; n = 4/ time pt NS; Adult; n = 8 US Tol: Not established. EMA established MRL: 500 ppb (liver, muscle, fat); 1000 ppb (kidney); 200 ppb (milk). NS NS NS IM 10 mg/kg Dihydro-streptomycin combined with benzyl-penicillin daily 3 Liver <400 ppb @ 14 days 14 days Healthy NS [25] 2005
Kidney <400 ppb @ 14 days 14 days
Muscle <400 ppb @ 14 days 14 days
Fat <400 ppb @ 14 days 14 days
Inj. Site 18 days (0.58 ppm) 28 days
HPLC NS 50 ppb IM 10 mg/kg Dihydro-streptomycin sulfate combined with 10 mg/kg streptomycin daily 3 Milk 48 h (0.06 ppm) 60 h Healthy Lactating
Dihydro-strepto-mycin Sheep; Suffolk & Suffolk/Cheviot; adult; n = 8 US Tol: Not established. EMA established MRL: 200 ppb (milk). HPLC 0.02 ppm 0.05 ppm IM 10 mg/kg Dihydro-streptomycin combined with 10 mg/kg streptomycin daily 3 Milk 48 h (0.06 ppm) 60 h Healthy Lactating; Milked 2×/day [26] 2002
Dihydro-strepto-mycin Sheep; NS; NS; n = 12 study; n = 4/time pt US Tol: Not established. EMA established MRL: 500 ppb (liver, muscle, fat); 1000 ppb (kidney). NS NS 400 ppb IM 10 mg/kg Dihydro-streptomycin combined w/ benzyl-penicillin daily 3 Liver 14 days Healthy NS [30] 2000
Kidney 14 days
Muscle 14 days
Fat 14 days
Inj. Site 18 days (0.584 ppm) 28 days
Dihydro-strepto-mycin Sheep; NS; NS; n = 12 study; n = 4/time pt US Tol: Not established. EMA established MRL: 500 ppb (liver, muscle, fat); 1000 ppb (kidney). HPLC NS 400 ppb IM 10 mg/kg Dihydro-streptomycin combined w/ procaine penicillin daily 3 Liver 14 days Healthy NS [31] 1998
Kidney 14 days
Muscle 14 days
Fat 14 days
Inj. Site 18 days (0.584 ppm) 28 days
Gentamicin Sheep; mixed breed; adult; n = 7 US Tol: Not established. EMA established MRL in all mammalian food producing species: 750 ppb (kidney). Bioassay NS NS IV 4 mg/kg Gentamicin 1 Kidney *biopsy 28 days (9.9 ppm) 35 days Healthy NS [32] 1985
Gentamicin Sheep; Suffolk; adult; n = 9 study; n = 3/time pt US Tol: Not established. EMA established MRL in all mammalian food producing species: 750 ppb (kidney); 50 ppb (muscle). Immuno-assay 0.01 ppm NS IM 3 mg/kg Gentamicin sulfate at 8 h intervals 2 Kidney 15 days (20.0 ppm §) >15 days Healthy NS [12] 1985
Muscle 15 days (0.21 ppm §) >15 days
Heart 15 days (0.64 ppm §) >15 days
Gentamicin Sheep; Suffolk; adult; n = 12 study; n = 3/time pt US Tol: Not established. EMA Established MRL in all mammalian food producing species: 200 ppb (liver); 750 ppb (kidney); 50 ppb (muscle, fat). Immuno-assay 0.01 ppm NS IM 2 mg/kg Gentamicin sulfate 1 Liver 12 days (0.31 ppt) >12 days Healthy NS [13] 1986
Kidney 12 days (2.74 ppt) >12 days
Muscle 12 days (0.2 ppt) >12 days
Inj. Site 12 days (0.15 ppt) >12 days
6 mg/kg Gentamicin sulfate 1 Liver 12 days (1.5 ppt) >12 days
Kidney 12 days (5.15 ppt) >12 days
Muscle 12 days (0.002 ppt) >12 days
Inj. Site 12 days (0.02 ppt) >12 days
18 mg/kg Gentamicin sulfate 1 Liver 12 days (4.0 ppt) >12 days
Kidney 12 days (9.23 ppt) >12 days
Muscle 12 days (0.14 ppt) >12 days
Inj. Site 12 days (0.53 ppt) >12 days
2 mg/kg Gentamicin sulfate at 8 h intervals 9 Liver 12 days (4.02 ppt) >12 days
Kidney 12 days (9.74 ppt) >12 days
Muscle 12 days (0.04 ppt) >12 days
Inj. Site 12 days (2.49 ppt) >12 days
6 mg/kg Gentamicin sulfate daily 3 Liver 12 days (3.12 ppt) >12 days
Kidney 12 days (10.0 ppt) >12 days
Muscle 12 days (0.14 ppt) >12 days
Inj. Site 12 days (5.03 ppt) >12 days
Gentamicin Sheep; western range; adult; n = 4 US Tol: Not established. EMA established MRL in all mammalian food producing species: 750 ppb (kidney). Immuno-assay 0.04 ppm NS IM 3 mg/kg Gentamicin sulfate at 12 h intervals 20 Kidney (biopsy) 77 days (9.71 ppm) >77 days NS NS [14] 1988
Kanamycin Sheep; Bergamo; adult; n = 12 study; n = 3/time pt US Tol: Not established. EMA established MRL: 600 ppb (liver); 2500 ppb (kidney); 100 ppb (muscle). Bioassay NS NS IM 20 mg/kg Kanamycin 1 Liver 3 days (2.2 ppm) 6 days NS NS [33] 1991
Kidney 10 days (8.31 ppm) 14 days
Muscle ND @ 3 days 3 days
Neomycin Goat; NS; NS; n = 18 study; n = 4/ time pt US Tol: 3600 ppb (liver); 7200 ppb (kidney);1200 ppb (muscle); 7200 ppb (fat). EMA MRL extrapolated to all food producing species: 5500 ppb (liver); 9000 ppb (kidney); 500 ppb (muscle, fat). Bioassay NS 0.5 ppm POMW 22 mg/kg Neomycin sulfate daily 14 Liver ND @ 12 h 12 h Healthy NS [15] 1996
Kidney 96 h (0.6 ppm) >96 h
Muscle ND @ 12 h 12 h
Fat ND @ 12 h 12 h
Neomycin Goat; NS; NS; n = 20 study; n = 5/time pt US Tol: 3600 ppb (liver); 7200 ppb (kidney); 1200 ppb (muscle); 7200 ppb (fat). EMA MRL extrapolated to all food producing species: 5500 ppb (liver); 9000 ppb (kidney); 500 ppb (muscle, fat). Bioassay NS 500 ppb POMW 20 mg/kg Neomycin sulfate daily 14 Liver ND @ 12 h 12 h Healthy NS [16] 2000
Kidney 96 h (700 ppb) >96 h
Muscle ND @ 12 h 12 h
Fat ND @ 12 h 12 h
Neomycin Goat; NS; NS; n = 20 study, n = 4/time pt US Tol: 3600 ppb (liver); 7200 ppb (kidney); 1200 ppb (muscle); 7200 ppb (fat). EMA MRL extrapolated to all food producing species: 5500 ppb (liver); 9000 ppb (kidney); 500 ppb (muscle, fat). Bioassay NS 0.5 ppm PO 22 mg/kg Neomycin sulfate daily 14 Liver ND @ 12 h 12 h Healthy NS [17] 1995
Kidney 96 h (0.7 ppm) >96 h
Muscle ND @ 12 h 12 h
Fat ND @ 12 h 12 h
Neomycin Goat; NS; NS; n = 20 study, n = 4/time pt US Tol: 3600 ppb (liver); 7200 ppb (kidney); 1200 ppb (muscle); 7200 ppb (fat). EMA MRL extrapolated to all food producing species: 5500 ppb (liver); 9000 ppb (kidney); 500 ppb (muscle, fat). NS NS 0.5 ppm POMW 22 mg/kg Neomycin sulfate daily 14 Liver ND @ 12 h 12 h Healthy NS [34] 1996
Kidney 96 h (0.57 ppm) >96 h
Muscle ND @ 12 h 12 h
Fat ND @ 12 h 12 h
Neomycin Sheep; NS; NS; n = 18 study; n = 4/time pt US Tol: 3600 ppb (liver); 7200 ppb (kidney); 1200 ppb (muscle); 7200 ppb (fat). EMA MRL extrapolated to all food producing species: 5500 ppb (liver); 9000 ppb (lidney); 500 ppb (muscle, fat). Bioassay NS 0.5 ppm POMW 22 mg/kg Neomycin sulfate daily 14 Liver ND @ 1 day 1 day Healthy NS [15] 1996
Kidney 1 day (female) (1.28 ppm) 3 days (female)
Kidney 3 days (male) (0.45 ppm) 7 days (male)
Muscle ND @ 1 day 1 day
Fat ND @ 1 day 1 day
Neomycin Sheep; NS; NS; n = 20 study; n = 5/time pt US Tol: 3600 ppb (liver); 7200 ppb (kidney); 1200 ppb (muscle); 7200 ppb (fat). EMA MRL extrapolated to all food producing species: 5500 ppb (liver); 9000 ppb (kidney); 500 ppb (muscle, fat). Bioassay NS 500 ppb POMW 20 mg/kg Neomycin sulfate daily 14 Liver ND @ 1 day 1 day Healthy NS [16] 2000
Kidney 3 days (522 ppb) 7 days
Muscle ND @ 1 day 1 day
Fat ND @ 1 day 1 day
Neomycin Sheep; NS; NS; n = 20 study, n = 4/time pt US Tol: 3600 ppb (liver); 7200 ppb (kidney); 1200 ppb (muscle); 7200 ppb (fat). EMA MRL extrapolated to all food producing species: 5500 ppb (liver); 9000 ppb (kidney); 500 ppb (muscle, fat). Bioassay NS 0.5 ppm PO 22 mg/kg Neomycin sulfate daily 14 Liver ND @ 1 day 1 day Healthy NS [17] 1995
Kidney 3 days (522 ppb) 7 days
Muscle ND @ 1 day 1 day
Fat ND @ 1 day 1 day
Neomycin Sheep; NS; NS; n = 20 study, n = 4/time pt US Tol: 3600 ppb (liver); 7200 ppb (kidney); 1200 ppb (muscle); 7200 ppb (fat). EMA MRL extrapolated to all food producing species: 5500 ppb (liver); 9000 ppb (kidney); 500 ppb (muscle, fat). NS NS 0.5 ppm POMW 22 mg/kg Neomycin sulfate daily 14 Liver ND @ 1 day 1 day Healthy NS [34] 1996
Kidney 1 day (female) (1.28 ppm) 3 days (female)
Kidney 3 days (male) (0.45 ppm) 7 days (male)
Muscle ND @ 1 day 1 day
Fat ND @ 1 day 1 day
Strepto-mycin Sheep; NS; NS; n = 4 US Tol: Not established. EMA established MRL: 200 ppb (milk). HPLC NS 50 ppb IM 10 mg/kg Streptomycin combined w/ dihydro-streptomycin daily 3 Milk 48 h (0.07 ppm) 60 h Healthy Lactating, Milked 2×/day [25] 2005
Strepto-mycin Sheep; Suffolk & Suffolk/Cheviot; adult; n = 8 US Tol: Not established. EMA established MRL: 200 ppb (milk). HPLC 0.02 ppm 0.05 ppb († 0.05 ppm) IM 10 mg/kg Streptomycin combined w/ dihydro-streptomycin daily 3 Milk 48 h (0.07 ppm) 60 h Healthy Milked 2×/day [26] 2002
Strepto-mycin Sheep; NS; NS; NS US Tol: Not established. EMA established MRL: 500 ppb (liver, muscle, fat); 1000 ppb (kidney). HPLC NS 200 ppb IM 10 mg/kg Streptomycin daily 3 Liver 2 days (655 ppb) >2 days Healthy NS [30] 2000
Kidney 2 days (914 ppb) >2 days
Muscle ND @ 2 days 2 days
Fat ND @ 2 days 2 days
Inj. Site 2 days (1373 ppb) >2 days

† Manuscript states limit of quantitation as 0.05 ppb; however, the limit of detection is in parts per million, therefore it is likely an error and should be interpreted as 0.05 parts per million. # = number. * Projected time for which residues could still be detected based on study protocol for sample collection time points and sample concentration results. Authors caution readers to critically evaluate these publications to estimate when full residue depletion might occur. Abbreviations: 2×/day: twice daily. LOD: Limit of detection. LOQ: Limit of quantification. EMA: European Medicines Agency. MRL: Maximum residue limit. ND: Not detected. NS: Not specified. Routes of Administration: IMM = intramammary, IM = intramuscular, IV = intravenous, PO = per os, POMF = per os as medicated feed, POMW = per os as medicated water, SC = subcutaneous. § Data points manually extracted use scanning software (Webplot digitizer or UnScanIt 7.0). Units: s = seconds, min = minutes, h = hours, ppt = parts per trillion, ppb = parts per billion, ppm = parts per million.

Amphenicol residues in milk or edible tissue samples from sheep or goats following treatment.

Analyte Species; Breed; Age; # of Animals per Time Point Tolerance/ MRL Analytical Method LOD LOQ Route of Admin-istration Dose & Active Ingredient # of Doses Matrix Last Sampling Time Point (Post-Last Treatment) When Residues WERE Detected Sampling Time Point When NO Residues Were Detected (Post-Last Treatment) * Health Status Additional Information Source/ Year
Chloram-phenicol Sheep; Awassi; adult; n = 2 US Tol: Not established. EMA MRL: Not established. Chemically NS NS IM 50 mg/kg Chloramphenicol 1 Milk 26 h (1.68 ppm §) >26 h Healthy Lactating [39] 1973
Milk 26 h (1.82 ppm §) >26 h Diseased-mastitis
Bioassay NS NS IM 50 mg/kg Chloramphenicol 1 Milk 26 h (1.02 ppm §) >26 h Healthy
Milk 26 h (1.54 ppm §) >26 h Diseased-mastitis
Radio-activity NS NS IM 50 mg/kg Chloramphenicol (radiolabeled) 1 Milk 13 h (NS) >13 h Healthy
Milk 13 h (NS) >13 h Diseased-mastitis
Chloramphenicol Sheep; Awassi; adult; n = 1 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IV 50 mg/kg Chloramphenicol sodium succinate then 12.5 mg/kg for 2 doses at 90 min interval 3 Milk 24 h (0.65 ppm §) 36 h Healthy Lactating; Milked 2x/day [24] 1973
Radio-activity NS NS IV 50 mg/kg Chloramphenicol (radiolabeled) then 12.5 mg/kg for 2 doses at 90 min interval 3 Milk 48 h (0.81 ppm §) 60 h
Chloram-phenicol Sheep; Awassi; Adult; n = 2 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IM 50 mg/kg Chloramphenicol 1 Milk 56 h (0.85 ppm §) >56 h Healthy Lactating; Milked 2×/day [29] 1974
Milk 56 h (1.28 ppm §) >56 h Diseased-mastitis
Radio-activity NS NS IM 50 mg/kg Chloramphenicol (radiolabeled) 1 Milk 56 h (0.2 ppm §) >56 h Healthy
Milk 56 h (0.18 ppm §) >56 h Diseased-mastitis
Chloram-phenicol Sheep; Rouge de L’Ouest; adult; n = 11 study; n = 3 & 2/time pt US Tol: Not established. EMA MRL: Not established. HPLC 2 ppb NS IM 30 mg/kg Chloramphenicol 1 Liver 24 h (0.35 ppb §) 336 h NS NS [40] 1990
Kidney 336 h (0.76 ppb §) >336 h
Muscle 336 h (2.13 ppb §) >336 h
Inj. Site 336 h (4.18 ppb §) >336 h
Chloram-phenicol Sheep; Awassi; adult; n = 2 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IV 50 mg/kg Chloramphenicol sodium succinate 1 Milk NS NS Healthy Lactating; Milked 2×/day [41] 1975
Florfenicol amine Sheep; Polypay; NS; n = 25 study; n = 5/time pt US Tol: Not established. EMA MRL by extension from bovine to ovine: 3000 ppb (liver); 300 ppb (kidney); 200 ppb (muscle). HPLC NS NS SC 40 mg/kg Florfenicol daily 3 Liver 40 days (1.99 ppm) >40 days NS NS [42] 2006
Kidney 40 days (0.17 ppm) >40 days
Muscle 40 days (0.08 ppm) >40 days
Fat 40 days (0.01 ppm) >40 days
Inj. Site 40 days (0.15 ppm) >40 days
Florfenicol amine Sheep; mixed breed; 6–7 months; n = 26 study; n = 5/time pt US Tol: Not established. EMA MRL by extension from bovine to ovine: 3000 ppb (liver); 300 ppb (kidney); 200 ppb (muscle). HPLC NS Liver: 0.32 ppm SC 40 mg/kg Florfenicol daily 3 Liver 40 days (NS) >40 days Healthy NS [43] 2008
Kidney: 0.1 ppm Kidney 40 days (NS) >40 days
Muscle: 0.05 ppm Muscle 40 days (NS) >40 days
Fat: 0.04 ppm Fat 40 days (NS) >40 days
Inj. Site: 0.05 ppm Inj. Site 40 days (NS) >40 days
Thiam-phenicol Sheep; crossbred; adult; n = 16 study; n = 4/time pt. US Tol: Not established. EMA MRL by extension from bovine to ovine: 50 ppb (liver, kidney, muscle, fat, milk). HPLC 5 ppb 21 ppb IM 30 mg/kg Thiamphenicol daily 5 Liver ND @ 4 days 4 days Healthy NS [44] 2000
Kidney 4 days (40.2 ppb) 8 days
Muscle 4 days
Fat 4 days (342.5 ppb) 8 days
Chloram-phenicol Goat; Desi; 9–12 months; n = NS US Tol: Not established. EMA MRL: Not established. Colorimetric NS NS IM 10 mg/kg Chloramphenicol 1 Milk 24 h (2.16 ppm) 2 days Healthy Lactating [45] 1983
IM 30 mg/kg Chloramphenicol 1 Milk 96 h (3.33 ppm) >4 days Healthy
Chloram-phenicol Goat; NS; Adult; n = 2 US Tol: Not established. EMA MRL: Not established. HPLC 5 ppb NS IM 600 mg Chloram-phenicol 1 Milk 8 h (0.077 ppm) 1 day Healthy Lactating [46] 1980
IMM 600 mg Chloram-phenicol 1 Milk 24 h (0.026 ppm) 32 h Healthy
Thiam-phenicol Goat; Saanen & crossbred; adult; n = 6 US Tol: Not established. EMA MRL by extension from bovine to ovine: 50 ppb (liver, kidney, muscle, fat, milk). HPLC NS NS IV 50 mg/kg Thiamphenicol 1 Milk 12 h (4.92 ppm §) >12 h Healthy Late lactation [35] 1991
IM 50 mg/kg Thiamphenicol 1 Milk 12 h (4.90 ppm §) >12 h Healthy
Florfenicol Goat; Saanen & crossbred; adult; n = 10 US Tol: Not established. EMA MRL: Not established. HPLC NS NS IV 25 mg/kg Florfenicol 1 Milk 8 h (0.21 ppm §) >8 h Healthy Mid-lactation [36] 1991
IM 25 mg/kg Florfenicol 1 Milk 8 h (0.11 ppm §) >8 h Healthy

§ Data points manually extracted use scanning software (Webplot digitizer or UnScanIt 7.0). # = number. * Projected time for which residues could still be detected based on study protocol for sample collection time points and sample concentration results. Authors caution readers to critically evaluate these publications to estimate when full residue depletion might occur. Abbreviations: 2×/day: twice daily. LOD: Limit of detection. LOQ: Limit of quantification. EMA: European Medicines Agency. MRL: Maximum residue limit. ND: Not detected. NS: Not specified. Routes of Administration: IMM = intramammary, IM = intramuscular, IV = intravenous, PO = per os, POMF = per os as medicated feed, SC = subcutaneous. Units: s = seconds, min = minutes, h = hours, ppb = parts per billion, ppm = parts per million.

Penicillin and penicillin-derivative residues in milk or edible tissue samples from sheep or goats following treatment.

Analyte Species; Breed; Age; # of Animals Tolerance/MRL Analytical Method LOD LOQ Route of Admin-istration Dose & Active Ingredient # of Doses Matrix Last Sampling Time Point (Post-Last Treatment) When Residues WERE Detected Sampling Time Point When NO Residues Were Detected (Post-Last Treatment) * Health Status Additional Information Source/ Year
Amoxicillin Sheep; Texel; adult; n = 12 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IM 10 mg/kg Amoxicillin sodium 1 Milk 500 min (0.03 ppm §) >500 min Healthy & Diseased- mastitis Lactating [47] 1979
Amoxicillin Goats; Saanen; adult; n = 6 US Tol: Not established. EMA MRL: Not established. Bioassay 0.001 ppm NS IMM 200 mg Amoxicillin trihydrate; 50 mg potassium clavulanate; 10 mg prednisolone combo product at 8 h intervals 3 Milk 5 days (0.07 ppm §) >5 days Healthy Lactating; Milked 2×/day; 1 syringe/ gland [49] 1989
Amoxicillin Sheep; Texel; adult; n = 12 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IM 10 mg/kg Amoxicillin trihydrate 1 Milk 500 min (0.06 ppm §) >500 min Healthy & Diseased- mastitis Lactating [47] 1979
Amoxicillin Sheep; Friesland; adult; n = 6 US Tol: Not established. EMA MRL: Not established. Bioassay 0.001 ppm NS IMM 200 mg Amoxicillin trihydrate; 50 mg potassium clavulanate; 10 mg prednisolone combo product at 8 h intervals 3 Milk 7 days (0.003 ppm §) >7 days Healthy Lactating; Milked 2×/day; 1 syringe/ gland [51] 1989
Amoxicillin Sheep; Comisana; adult; n = 10 US Tol: Not established. EMA MRL: Not established. HPLC 1.5 ppb 2.5 ppb IM 12.5 mg/kg Amoxicillin trihydrate (long acting) 1 Milk 132 h (1.5 ppb) 6 days Healthy Lactating; Milked 2×/day [57] 2002
Amoxicillin Sheep; domestic dairy breed; adult; n = 10 US Tol: Not established. EMA MRL: Not established. Bioassay 3 ppb 4 ppb IMM w/ IM 200 mg Amoxicillin trihydrate, 50 mg potassium clavulanate, 10 mg prednisolone combination product (IMM) at 12 h intervals co-administered with 140 mg/35 mg per mL amoxicillin trihydrate/ clavulanic acid (IM) at 24 h intervals 5 (IMM); 2(IM) Milk 192 h (4.5 ppb) >192 h Diseased- mastitis Lactating; 1 syringe/gland [52] 2009
Amoxicillin Sheep; crossbred; NS; n = 36 study; n = 4/time pt Dairy type; adult; n = 20 US Tol: Not established. EMA MRL: Not established. LC-MS 5.8 ppb 25.6 ppb IM 7 mg/kg Amoxicilllin † daily 5 Liver NS 48 h Healthy NS [48] 2012
Kidney NS 48 h
Muscle NS 48 h
Fat NS 48 h
Inj. Site 64 days (25.6 ppb) >64 days
NS NS NS IM 7 mg/kg Amoxicilllin † daily 5 Milk 120 h (2.09 ppb) >120 h Healthy Lactating; Milked 2×/day
Ampicillin Sheep; Texel; adult; n = 12 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IM 10 mg/kg Ampicillin sodium 1 Milk 8 h (0.03 §) >8 h Healthy Lactating [47] 1979
10 h (0.03 §) >10 h Diseased- mastitis
Ampicillin Goats; Saanen; adult; n = 24 study US Tol: Not established. EMA MRL: Not established. HLPC 1.5 ppb 2.2 ppb IM 15 mg/kg Amoxicilllin † (long acting) at 72 h interval 2 Milk 168 h (6.0 ppb) 180 h Healthy Mid-lactation; Milked 2×/day [54] 2010
Ampicillin Sheep; Texel; adult; n = 12 US Tol: Not established EMA MRL: Not established. Bioassay NS NS IM 10 mg/kg Ampicillin trihydrate 1 Milk 12 h (0.04 ppm §) >12 h Healthy Lactating [47] 1979
12 h (0.1 ppm §) >12 h Diseased- mastitis
Ampicillin Sheep; NS; adult; n = 4 US Tol: Not established. EMA MRL: Not established. NS NS NS IMM 250,000 IU Ampicillin trihydrate 1 Milk 72 h (0.11 ppm) 96 h NS Lactating; Half syringe per gland [58] 1977
Cloxacillin Goats; Saanen; adult; n = 8 US Tol: Not established. EMA MRL: Not established. Bioassay 0.02 ppm NS IMM 200 mg Cloxacillin at 48 h intervals 3 Milk 13 h (0.15 ppm§) >13 h Healthy Late lactation; Milked 2×/day. Only one half/gland treated. [53] 1984
Diclox-acillin Sheep; Sarda; 2–3.5 years; n = 4 US Tol: Not established. EMA MRL: Not established. HPLC NS 0.02 ppm IMM 100 mg/half Dicloxacillin at 12 h intervals. 3 Milk 60 h (0.029 ppm) 72 h Healthy Lactating, High production; Milked 2x/day [50] 2000
72 h (0.026 ppm) 84 h Healthy Lactating, Low production; Milked 2×/day
Nafcillin Goats; NS; Adults; n = 220 US Tol: Not established. EU MRL by extension from bovine to all ruminants: 30 ppb (milk). Bioassay 0.012 ppm 0.015 ppm IMM 300,000 IU Procaine benzylpenicillin; 100 mg dihydro-streptomycin; 100 mg nafcillin 1 Milk NS 3 days Healthy Dry off period (mean 61.0 ± 14.3 days SD (range 23–156 days); 1 tube per gland before drying off. Sample collected after kidding [27] 1995
Nafcillin Sheep; Lacaune; adult; n = 8 US Tol: Not established. EMA MRL by extension from bovine to all ruminants: 30 ppb (milk). Bioassay 0.02 ppm NS IMM 300,000 IU Procaine benzylpenicillin; 100 mg dihydrostreptomycin; 100 mg nafcillin 1 Milk ND 2 days Healthy Dry off period (mean 112 days (range 85–223 days); 1 tube per gland before drying off. Sample collected after lambing [28] 1995
Pen-ethamate Goats; NS; Adult; n = 2 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IM 200,000 IU Penethamate (oil) 200,000 IU Penethamate (aqueous) 1 Milk 1 day (0.004 U/mL) >1 day NS Lactating [59] 1966
Milk 12 h (0.075 U/mL) 1 day
IM 500,000 IU Penethamate (oil) 500,000 IU Penethamate (aqueous) 1 Milk 1 day (0.04 U/mL) >1 day
Milk 1 day (0.2 U/mL) >1 day
Penicillin Sheep; Awassi; Adult; n = 2 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IM 20 mg/kg Penicillin † 1 Milk 12 h (0.02 ppm §) 1 day Healthy Lactating [29] 1974
Radioactivity NS NS Milk 56 h (0.03 ppm §) >56 h Diseased- mastitis
Bioassay NS NS IM 20 mg/kg Benzylpenicillin-14C 1 Milk 48 h (0.01 ppm §) 56 h Healthy
Radioactivity NS NS Milk 12 h (0.02 ppm §) 1 day Diseased- mastitis
Penicillin Goats; NS; Adult; n = 2 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IM 200,000 IU Procaine penicillin (oil) 1 1 Milk 1 day (0.008 U/mL) >1 day NS Lactating [59] 1966
200,000 IU Procaine penicillin (aqueous) Milk 12 h (0.012 U/mL) 1 day
IM 500,000 IU Procaine penicillin (oil) Milk 1 day (0.07 U/mL) >1 day
500,000 IU Procaine penicillin (aqueous) Milk 1 day (0.02 U/mL) >1 day
Penicillin Goats; NS; Adults; n = 217 US Tol: Not established. EMA MRL: Not established. Bioassay 0.002 IU/mL 0.004 IU/mL IMM 300,000 IU Procaine benzylpenicillin; 100 mg dihydro-streptomycin; 100 mg nafcillin combo product 1 Milk NS 7 days Healthy Dry off period (mean 61.0 ± 14.3 days SD (range 23–156 days). 1 tube per gland before drying off. Sample collected after kidding [27] 1995
Penicillin Goats; dairy type; 2–7 years; n = 10 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IMM 100,000 IU Penicillin G procaine at 12 h intervals 3 Milk 60 h (0.49 ppm §) >60 h Healthy Early & mid-lactation; Milked 2x/day; 1 syringe per gland [60] 1984
Penicillin Sheep; NS; NS; n = 2 US Tol: Zero. EMA MRL: Not established. LC-MS 0.005 ppm NS IM 1500 mg Benzylpenicillin daily 3 Liver 2 days (0.24 ppm) >2 days NS NS [56] 1996
Kidney 2 days (0.87 ppm) >2 days
Muscle 2 days (0.02 ppm) >2 days
Penicillin Sheep; Lacaune; adult; n = 8 US Tol: Zero. EMA MRL: Not established. Bioassay 0.006 ppm NS IMM 300,000 IU Procaine benzylpenicillin; 100 mg dihydro-streptomycin; 100 mg nafcillin 1 Milk 3 days (0.01 ppm §) 4 days Healthy Dry off period (mean 112 days (range 85–223 days); 1 tube per gland before drying off. Sample collected after lambing [28] 1995
Penicillin Sheep; NS; 14–17 months; n = 10 study; n = 10/time pt US Tol: Zero. EMA MRL: Not established. Bioassay 0.0125 ppm NS IM 3000 IU/lb Penicillin G procaine daily 4 Liver NS 9 days Healthy NS [61] 2010
Kidney NS 9 days
Muscle NS 9 days
Fat NS 9 days
Inj. Site NS 9 days
Penicillin Sheep; Awassi; adult; n = 3 US Tol: Zero. EMA MRL: Not established. Bioassay NS NS IV 20 mg/kg Penicillin †, then 10 mg/kg for 4 doses 45 min interval 5 Milk 36 h (0.01 ppm §) 48 h Healthy Lactating; Milked 2×/day [24] 1973
Radioactivity NS NS IV 20 mg/kg Penicillin † (radiolabeled) then 10 mg/kg for 4 doses 45 min interval 5 Milk 8 h (0.08 ppm §) 10 h
Penicillin Sheep; Sardinian; Adult; n = 5 US Tol: Zero. EMA MRL: Not established. HPLC 2.6 ppb 8.8 ppb IM 24 mg/kg Penicillin G sodium 1 Milk 8 days (0.01 ppm) > 8 days NS Lactating; Milked 2×/day [55] 1998
IMM 24 mg/kg Penicillin G sodium 1 Milk 7 days (0.001 ppm) 8 days
Penicillin Sheep; domestic dairy breed; adult; n = 10 US Tol: Zero. EMA MRL: Not established. Bioassay 3 ppb 4 ppb IMM co-admin w/IM 1,000,000 IU Benzylpenicillin (IMM) daily co- administered with 250,000 IU benzylpenicillin (IM) at 24 h intervals. 5 (IMM) 2 (IM) Milk 192 h (9.9 ppb) >192 h Diseased Lactating; 1 syringe/gland [52] 2009

† Salt form unclear or not stated in article. # = number. * Projected time for which residues could still be detected based on study protocol for sample collection time points and sample concentration results. Authors caution readers to critically evaluate these publications to estimate when full residue depletion might occur. § Data points manually extracted use scanning software (Webplot digitizer or UnScanIt 7.0). Abbreviations: 2×/day: twice daily. LOD: Limit of detection. LOQ: Limit of quantification. EMA: European Medicines Agency. MRL: Maximum residue limit. ND: Not detected. NS: Not specified. Routes of Administration: IMM = intramammary, IM = intramuscular, IV = intravenous, PO = per os, POMF = per os as medicated feed, SC = subcutaneous. Units: s = seconds, min = minutes, h = hours, ppb = parts per billion, ppm = parts per million, mL = milliliter.

Cephalosporin residues in milk or edible tissue samples from sheep or goats following treatment.

Analyte Species; Breed; Age; # of Animals Tolerance/MRL Analytical Method LOD LOQ Route of Admini-stration Dose & Active Ingredient # of Doses Matrix Last Sampling Time Point (Post-Last Treatment) When Residues WERE Detected Sampling Time Point When NO Residues Were Detected (Post-Last Treatment) * Health Status Additional Information Source/Year
Cefepime Goat; NS; Adult; n = 10 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IV 20 mg/kg Cefepime 1 Milk 12 h (0.17 ppm) >12 h Healthy Lactating; Milked 2×/day [62] 2004
IM 20 mg/kg Cefepime 1 Milk 12 h (0.25 ppm) >12 h
Cefepime Goat; NS; 1 year; n = 5 US Tol: Not established. EMA MRL: Not established. HPLC 1.15 ppb 3.49 ppm IM 50 mg/kg Cefepime 1 Milk 4 h (5.14 ppm§) > 4 h Healthy Lactating [72] 2010
Cefonicid Goat; Muriano-Granadina; 2–4 years; n = 6 US Tol: Not established. EMA MRL: Not established. HPLC 500 ppb 750 ppb IV 10 mg/kg Cefonicid sodium 1 Milk 1 h Healthy Lactating; Milked 1×/day [63] 2020
IM 10 mg/kg Cefonicid sodium 1 Milk 1 h
SC 10 mg/kg Cefonicid sodium 1 Milk 1 h
SC 20 mg/kg Cefonicid sodium 1 Milk 1 h
Cef-quinome Goat; Zaraibi; 30–36 months; n = 5 US Tol: Not established. EMA MRL: Not established. Bioassay 0.009 ppm 0.027 ppm IV 3 mg/kg Cefquinome sulfate 1 Milk 48 h (0.02 ppm §) >2 days Healthy Lactating; Milked 1×/day [67] 2015
HPLC 0.006 ppm 0.017 ppm Milk 48 h (0.01 ppm §) >2 days
Bioassay 0.009 ppm 0.027 ppm IV 3 mg/kg Cefquinome sulfate 1 Milk 48 h (0.02 ppm §) >2 days Diseased-Mastitis
HPLC 0.006 ppm 0.017 ppm Milk 48 h (0.02 ppm §) >2 days
Cef-quinome Goat; Zaraibi; 30–36 months; n = 5 US Tol: Not established. EMA MRL: Not established. HPLC 0.006 ppm 0.018 ppm IMM 75 mg Cefquinome sulfate 1 Milk 120 h (0.01 ppm §) >120 h Healthy Early & mid-lactating; 1 full tube per gland 1 full tube into single infected udder half [68] 2019
IMM 75 mg Cefquinome sulfate 1 Milk 96 h (0.01 ppm §) 120 h Diseased-Mastitis
Cef-tazidime Goat; Creole; Adult; n = 6 US Tol: Not established. EMA MRL: Not established. Bioassay 0.125 ppm 0.3 ppm IV 10 mg/kg Ceftazidime 1 Milk 12 h (0.52 ppm §) >12 h Healthy Lactating; Milked 2x/day [73] 2011
IM 10 mg/kg Ceftazidime 1 Milk 12 h (0.54 ppm §) >12 h
Ceftiofur Goat; Alpine & Alpine-Saanen; 4 years; n = 6 US Tol: 100 ppb (milk). EMA MRL extrapolated from bovine to all mammalian species: 100 ppb (milk). HPLC NS 0.05 ppm IV 2.2 mg/kg Ceftiofur sodium 1 Milk 24 h (NS) 2 days Healthy Lactating; Milked 2×/day [71] 1994
IM 2.2 mg/kg Ceftiofur sodium daily 5 Milk 24 h (NS) 2 days
Ceftiofur Sheep; NS; Adult; n = 9 US Tol: 100 ppb (milk). EMA MRL by extension from bovine to ovine: 100 ppb (milk). HPLC NS NS IM 2 mg/kg Ceftiofur sodium daily 5 Milk 12 h Healthy Lactating [74] 2006
Ceftiofur Goat; mixed dairy type; 28 months; n = 5 US Tol: 100 ppb (milk). EMA MRL extrapolated from bovine to all mammalian species: 100 ppb (milk). LC-MS NS 20 ppb IMM 125 mg Ceftiofur hydrochloride daily 2 Milk 72 h (37 ppb) 4 days Healthy Mid- & late lactation; Milked 2×/day. Left udder half infused. [75] 2015
Ceftriaxone Goat; Dairy type; 1.5–2 years; n = 6 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IV 20 mg/kg Ceftriaxone sodium 1 Milk 2 h (0.11 ppm) 2.5 h Healthy Lactating [64] 2013
Ceftriaxone Goat; NS; 2–2.5 years; n = 10 US Tol: Not established. EMA MRL: Not established. Bioassay NS 0.2 ppm IV 20 mg/kg Ceftriaxone 1 Milk 8 h (0.36 ppm) 10 h Healthy Lactating [65] 2005
IM 20 mg/kg Ceftriaxone 1 Milk 10 h (0.26 ppm) 12 h
Ceftriaxone Sheep; native breed; 2–3 years; n = 6 US Tol: Not established. EMA MRL: Not established. Bioassay NS 0.1 ppm IV 10 mg/kg Ceftriaxone 1 Milk 10 h (0.22 ppm) 12 h Healthy Lactating; Milked 2×/day [76] 2006
IM 10 mg/kg Ceftriaxone 1 Milk 12 h (0.19 (ppm) 24 h
Ceph-acetrile Sheep; Texel; adult; n = 6 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IM 12 mg/kg Benzathine cephacetrile 1 Milk 24 h (NS) >1 day Healthy Lactating [66] 1977
Cephalexin Goat; NS; 1 year; n = 2 US Tol: Not established. EMA MRL: Not established. HPLC 0.165 ppm NS IM 10 mg/kg Cephalexin 1 Milk 72 h (0.07 ppm §) >3 days NS Lactating [77] 2019
Cephalexin Sheep; Awassi; adult; n = 10 US Tol: Not established. EMA MRL: Not established. Bioassay 0.1 ppm NS IM 10 mg/kg Cephalexin 1 Milk 8 h (0.46 ppm §) >8 h Healthy Late lactation [69] 1988
Ceph-alothin Goat; Creole; adult; n = 20 US Tol: Not established. EMA MRL: Not established. HPLC 0.01 ppm NS IV 10 mg/kg Cephalothin 1 Milk 12 h (0.31 ppm §) >12 h Healthy Lactating; Milked 2x/day [78] 2004
Ceph-alothin Goat; Creole; adult; n = 22 study; groups of 8, 8 and 6 US Tol: Not established. EMA MRL: Not established. HPLC 0.01 ppm NS IV 20 mg/kg Cephalothin 1 Milk 6 h (0.08 ppm §) 8 h Healthy Early lactation; Restricted diet [79] 2007
IV 20 mg/kg Cephalothin 1 Milk 8 h (0.28 ppm §) 10 h Early lactation; Restricted diet + additional energy
IV 20 mg/kg Cephalothin 1 Milk 12 h (0.12 ppm §) 14 h Early lactation; Balanced diet
Cephapirin Goat; French Alpine; 1–7 years; n = 20 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IMM 200 mg Cephapirin at 12 h intervals 2 Milk ND @ 192 h 8 days Healthy Mid-lactation; 1 full tube into R half udder [70] 1986
IMM 200 mg Cephapirin at 12 h intervals 3 Milk ND @ 192 h 8 days
Cephapirin Goat; dairy type; 2–7 years; n = 10 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IMM 200 mg Sodium cephapirin at 12 h intervals 2 Milk 48 h (0.03 ppm §) 60 h Healthy Early & mid- lactation; Milked 2×/day; 1 full tube into each gland [60] 1984
Cephradine Goat; NS; adult; n = 4 US Tol: Not established. EMA MRL: Not established. Spectrophoto-metrically 0.2 ppm NS IM 10 mg/kg Cephradine 1 Milk 8 h (1.55 ppm) 12 h Healthy and Diseased Lactating [80] 1994
IM 10 mg/kg Cephradine at 12 h intervals 3 Milk 8 h (1.28 ppm) 12 h
IM 10 mg/kg Cephradine at 12 h intervals 5 Milk 8 h (3.02 ppm) 12 h
IM 10 mg/kg Cephradine at 12 h intervals 7 Milk 8 h (2.78 ppm) 12 h
IM 10 mg/kg Cephradine at 12 h intervals 9 Milk 8 h (3.02 ppm) 12 h

§ Data points manually extracted use scanning software (Webplot digitizer or UnScanIt 7.0). # = number. * Projected time for which residues could still be detected based on study protocol for sample collection time points and sample concentration results. Authors caution readers to critically evaluate these publications to estimate when full residue depletion might occur. Abbreviations: 1×/day: once daily. 2×/day: twice daily. LOD: Limit of detection. LOQ: Limit of quantification. EMA: European Medicines Agency. MRL: Maximum residue limit. ND: Not detected. NS: Not specified. Routes of Administration: IMM = intramammary, IM = intramuscular, IV = intravenous, SC = subcutaneous. Units: s = seconds, min = minutes, h = hours, ppb = parts per billion, ppm = parts per million.

Fluoroquinolone residues in milk or edible tissue samples from sheep or goats following treatment.

Analyte Species; Breed; Age; # of Animals Tolerance/ MRL Analytical Method LOD LOQ Route of Admini-stration Dose & Active Ingredient # of Doses Matrix Last Sampling Time Point (Post-Last Treatment) When Residues WERE Detected Sampling Time Point When NO Residues Were Detected (Post-Last Treatment) * Health Status Additional Information Source/ Year
Ciprofloxacin Goats; NS; adult; n = 6 US Tol: Prohibited. EMA MRL: Not established. Bioassay 0.05 ppm NS IV 4 mg/kg Ciprofloxacin 1 Milk 24 h (0.07 ppm) 30 h Healthy Lactating [81] 2014
Ciprofloxacin Goats; Baladi; 30–36 months; n = 5 US Tol: Prohibited. EMA MRL: Not established. Bioassay 0.01 ppm NS IV 5 mg/kg Ciprofloxacin 1 Milk 10 h (0.11 ppm) 18 h Healthy Lactating [82] 1998
IM 5 mg/kg Ciprofloxacin 1 Milk 10 h (0.07 ppm) 18 h
IM 5 mg/kg Ciprofloxacin daily 5 Milk 3 days (0.07 ppm) 4 days
Danofloxacin Goats; Murciano-Granadina; 1.5–3 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC 0.005 ppm 0.015 ppm SC 6 mg/kg Danofloxacin 1 Milk 36 h (0.01 ppm §) 48 h Healthy Mid-lactation; Milked 2×/day [83] 2007
Danofloxacin Sheep; Manchega; 2–4 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC 0.005 ppm 0.015 ppm SC 6 mg/kg Danofloxacin 1 Milk 36 h (0.02 ppm §) 48 h Healthy Mid-lactation; Milked 2×/day [83] 2007
Danofloxacin Sheep; Assaf; adult; n = 12 US Tol: Prohibited. EMA MRL: Not established. Bioassay 0.04 ppm NS IV 1.25 mg/kg Danofloxacin 1 Milk 24 h (0.1 ppm §) >1 day Healthy Mid-lactation [99] 1997
IM 1.25 mg/kg Danofloxacin 1 Milk 24 h (0.07 ppm §) >1 day
Danofloxacin Sheep; Assaf; 2–3 years; n = 5 US Tol: Prohibited. EMA MRL: Not established. HPLC 4 ppb 5 ppb IM 1.25 mg/kg 1 Milk 24 h (0.07 ppm §) >24 h Healthy Mid-lactation; Milked 2×/day [96] 2011
IM 1.25 mg/kg co-administered with 0.2 mg/kg ivermectin 1 Milk 24 h (0.09 ppm §) >24 h
Danofloxacin Sheep; Assaf; 2–3 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC 4 ppb 5 ppb IM 1.25 mg/kg Danofloxacin 1 Milk 24 h (0.08 ppm §) >24 h Healthy Mid-lactation; Milked 2×/day [97] 2013
IM 1.25 mg/kg Danofloxacin + soy diet 1 Milk 24 h (0.1 ppm §) >24 h
IM 1.25 mg/kg Danofloxacin + Gen-daid (isoflavones) 1 Milk 24 h (0.03 ppm §) >24 h
Danofloxacin Sheep; Assaf; 2–3 years; n = 6 US Tol: Prohibited EMA MRL: Not established. HPLC NS 100 ppb IM 1.25 mg/kg Danofloxacin 1 Milk 24 h (0.03 ppm §) >24 h Healthy Mid-lactation; Milked 2×/day [100] 2013
IM 1.25 mg/kg Danofloxacin co-administered with 1 mg/kg IV triclabendazole 1 Milk 24 h (0.25 ppm §) >24 h
Danofloxacin Sheep; Assaf; adult; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC NS 19 ppb IM 1.25 mg/kg Danofloxacin standard diet 1 Milk 24 h (0.05 ppm §) > 24 h Healthy Mid-lactation; Milked 2×/day [101] 2018
IM 1.25 mg/kg Danofloxacin w/ 10% flaxseed diet 1 Milk 24 h (0.04 ppm §) >24 hr
IM 1.25 mg/kg Danofloxacin w/ 15% flaxseed diet 1 Milk 24 h (0.05 ppm §) > 24 h
Difloxacin Goats; Murciano-Granadina; 4–5 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC NS 10 ppb IV 5 mg/kg Difloxacin 1 Milk 48 h (0.02 ppm §) 72 h Healthy Lactating; Milked 1×/day [102] 2010
SC 5 mg/kg Difloxacin 1 Milk 36 h (0.02 ppm §) 48 h
SC 15 mg/kg Difloxacin (long acting) 1 Milk 144 h (0.59 ppm §) >144 h
Difloxacin Goats; Murciano-Granadina; 4–5 years; n = 6 US Tol: Prohibited. EMA MRL: Not established HPLC NS 10 ppb SC 15 mg/kg Difloxacin (long acting) 1 Milk 144 h (0.07 ppm §) >144 h Healthy Lactating; Milked 1x/day [84] 2011
Enrofloxacin Goats; Sham; 2–3 years; n = 10 US Tol: Prohibited. EMA MRL extension from bovine to all food producing species: 100 ppb (milk). Bioassay NS 0.02 ppm IV 5 mg/kg Enrofloxacin 1 Milk 24 h (0.06 ppm) 36 h Healthy Mid-lactation; Milked 2x/day [85] 2003
IV 5 mg/kg Enrofloxacin co-administered with 7.5 mg/kg albendazole PO 1 Milk 12 h (0.11 ppm) 24 h
IM 5 mg/kg Enrofloxacin 1 Milk 36 h (0.08 ppm) 48 h
IM 5 mg/kg Enrofloxacin co-administered with 7.5 mg/kg albendazole PO 1 Milk 24 h (0.16 ppm) 36 h
Enrofloxacin Goats; Murciano-Granadina; 2.5–3.5 years; n = 6 US Tol: Prohibited. EMA MRL extension from bovine to all food producing species: 100 ppb (milk). HPLC NS NS SC 5 mg/kg Enrofloxacin 1 Milk NS NS † Healthy Lactating [103] 2009
Ciprofloxacin
Enrofloxacin Goats; Murciano-Granadina; 2.5–3.5 years; n = 6 US Tol: Prohibited. EMA MRL extension from bovine to all food producing species: 100 ppb (milk). HPLC NS NS IV 5 mg/kg Enrofloxacin 1 Milk NS NS ‡ Healthy Lactating [86] 2009
SC 5 mg/kg Enrofloxacin (long acting) 1 Milk NS NS Ϙ
Enrofloxacin Goats; NS; 1.5–2 years; n = 6 US Tol: Prohibited. EMA MRL extension from bovine to all food producing species: 100 ppb (milk). Bioassay 0.01 ppm NS SC 5 mg/kg Enrofloxacin 1 Milk 30 h (0.08 ppm) 36 h Healthy Lactating [87] 2009
SC 5 mg/kg Enrofloxacin SC, pretreated with 70 mg/kg probenecid PO 1 Milk 36 h (0.02 ppm) 48 h
Enrofloxacin Sheep; NS; Neo-natal US Tol: Prohibited. EMA MRL by extension from bovine to ovine: 300 ppb (liver); 200 ppb (kidney); 100 ppb (muscle, fat). HPLC NS 10 ppb PO 7.5 mg/kg Enrofloxacin 1 Liver NS Enro ֘: 16 days Healthy NS [104] 1998
Cipro ͌: 16 days
Kidney NS Enro ֘: 16 days
Cipro ͌: 16 days
Ciprofloxacin Muscle NS Enro ֘: 16 days
Cipro ͌: 16 days
Fat NS Enro ֘: 16 days
Cipro ͌: 16 days
Enrofloxacin Sheep; crossbred; 2–4 years; n = 6 US Tol: Prohibited. EMA MRL extension from bovine to all food producing species: 100 ppb (milk). Bioassay NS 0.018 ppm IV 2.5 mg/kg Enrofloxacin 1 Milk 24 h (0.13 ppm §) >24 h Healthy Lactating; Milked 2×/day [88] 2003
IM 2.5 mg/kg Enrofloxacin 1 Milk 24 h (0.15 ppm §) >24 h
Enrofloxacin Sheep; Assaf; 2–3 years; n = 12 US Tol: Prohibited. EMA MRL extension from bovine to all food producing species: 100 ppb (milk). HPLC NS NS IV 2.5 mg/kg Enrofloxacin 1 Milk 24 h (0.09 ppm §) > 24 h Healthy Mid-lactation; Milked 2×/day [98] 2006
IV 2.5 mg/kg Enrofloxacin co-administered with 0.8 mg/kg genistein IM 1 Milk 24 h (0.05 ppm §) > 24 h
IV 2.5 mg/kg Enrofloxacin co-administered with 2 mg/kg albendazole IV 1 Milk 24 h (0.06 ppm §) > 24 h
Ibafloxacin Goats; Murciano-Granadina; 3–4 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC NS 10 ppb IV 15 mg/kg Ibafloxacin 1 Milk 6 h (0.05 ppm §) 12 h Healthy Lactating [89] 2007
Levofloxacin Goats; NS; 3–5 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. Bioassay NS 0.05 ppm IV 4 mg/kg Levofloxacin hemihydrate 1 Milk 36 h (0.04 ppm §) 48 h Healthy Lactating [90] 2009
IM 4 mg/kg Levofloxacin hemihydrate 1 Milk 36 h (0.06 ppm §) 48 h
Marbo-floxacin Goats; Anglo-nubian; 3–5 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC NS 0.025 ppm IV 5 mg/kg Marbofloxacin 1 Milk 36 h (0.06 ppm §) 48 h Healthy Lactating [91] 2017
IM 5 mg/kg Marbofloxacin 1 Milk 36 h (0.07 ppm §) 48 h
Marbo-floxacin Sheep; Assaf; adult; n = 15 US Tol: Prohibited. EMA MRL: Not established. Bioassay 0.05 ppm ^ 0.04 ppm ^ IV 2.5 mg/kg Marbofloxacin 1 Milk 24 h (0.05 ppm §) >24 h Healthy Mid-lactation [92] 1997
IM 2.5 mg/kg Marbofloxacin 1 Milk 24 h (0.23 ppm §) > 24 h
Moxifloxacin Goats; Murciano-Granadina; 3–4 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC NS 10 ppb IV 5 mg/kg Moxifloxacin 1 Milk 32 h (0.01 ppm §) 48 h Healthy Lactating [93] 2006
SC 5 mg/kg Moxifloxacin 1 Milk 32 h (0.05 ppm §) 48 h
Moxifloxacin Goats; Murciano-Granadina; 3–4 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC NS 10 ppb IM 5 mg/kg Moxifloxacin 1 Milk 32 h (0.01 ppm §) 48 h Healthy Lactating [105] 2007
Norfloxacin Sheep; crossbred; adult; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC 0.07 ppm NS IV 25 mg/kg Norfloxacin nicotinate 1 Milk 24 h (10 ppm) >24 h Healthy Lactating [106] 1994
Orbifloxacin Goats; Murciano-Granadina; 5–6 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. HPLC 20 ppb 25 ppb IV 2.5 mg/kg Orbifloxacin 1 Milk 12 h (0.04 ppm §) 24 h Healthy Lactating [107] 2007
SC 2.5 mg/kg Orbifloxacin 1 Milk 24 h (0.03 ppm §) 36 h
IM 2.5 mg/kg Orbifloxacin 1 Milk 12 h (0.05 ppm §) 24 h
Orbifloxacin Sheep; Barky; 4–6 years; n = 6 US Tol: Prohibited. EMA MRL: Not established. Bioassay NS 0.04 ppm IV 2.5 mg/kg Orbifloxacin 1 Milk 24 h (0.09 ppm §) 30 h Healthy Lactating [94] 2009
IM 2.5 mg/kg Orbifloxacin 1 Milk 30 h (0.06 ppm §) 48 h
Pefloxacin Goats; Egyptian; 2 years; n = 5 US Tol: Prohibited. EMA MRL: Not established. Bioassay NS 0.078 ppm IV 10 mg/kg Pefloxacin 1 Milk 10 h (0.1 ppm) 12 h Healthy Lactating [95] 2002
IM 10 mg/kg Pefloxacin 1 Milk 10 h (0.1 ppm) 12 h
Flumequine Sheep US Tol: Not established. EMA established MRL: 100 ppb (liver); 300 ppb (kidney); 50 ppb (muscle, fat, skin). HPLC NS 100 ppb IM 12 mg/kg Flumequine for first dose, then 6 mg/kg at 12 h intervals 10 Liver Flu: 78 h (13.8 ppb) Flu: >78 h NS NS [108] 1997
7-OH: 48 h(10.24 ppb) 7-OH: 60 h
Kidney Flu: 78 h (38.6 ppb) Flu: >78 h
7-OH: 78 h (4.5 ppb) 7-OH: >78 h
Muscle Flu: 78 h (9.0 ppb) Flu: >78 h
7-Hydroxy-flumequine 7-OH: 18 h (15.3 ppb) 7-OH: 30 h
Fat Flu: 78 h (52.5 ppb) Flu: >78 h
7-OH: ND @ 18 h 7-OH: 18 h
Inj. Site Flu: 90 h (10 ppb) Flu: >90 h
7-OH: 30 h (13.5 ppb) 7-OH: 42 h
Flumequine Sheep; NS; NS; n = 20 study; n = 4/time pt US Tol: Not established. EMA established MRL: 100 ppb (liver); 300 ppb (kidney); 50 ppb (muscle, fat, skin). HPLC NS 5 ppb IM 12 mg/kg Flumequine for first dose, then 6 mg/kg at 12 h intervals 6 Liver 78 h (19.3 ppb) >78 h Healthy NS [109] 1998
Kidney 78 h (62.5 ppb) >78 h
Muscle 78 h (12.4 ppb) >78 h
Fat 78 h (171.9 ppb) >78 h

§ Data points manually extracted use scanning software (Webplot digitizer or UnScanIt 7.0). # = number. † Enrofloxacin parent half-life reported = 2.74 h; Ciprofloxacin metabolite half-life = 4.79 h. ‡ Intravenous half-life reported= 5.39 h. Ϙ Subcutaneous half-life reported= 14.85 h. ֘ Enro: Enrofloxacin. ͌ Cipro: Ciprofloxacin. * Projected time for which residues could still be detected based on study protocol for sample collection time points and sample concentration results. Authors caution readers to critically evaluate these publications to estimate when full residue depletion might occur. ^ LOD and LOQ values should be confirmed with authors; however, they are reported as published. Abbreviations: 1×/day: once daily. 2×/day: twice daily. 7-OH: 7-hydroxyflumequine. LOD: Limit of detection. LOQ: Limit of quantification. EMA: European Medicines Agency. FLU: flumequine. MRL: Maximum residue limit. NS: Not specified. Routes of Administration: IM = intramuscular, IV = intravenous, PO = per os, SC = subcutaneous. Units: s = seconds, min = minutes, h = hours, ppb = parts per billion, ppm = parts per million.

Macrolide residues in milk or edible tissue samples from sheep or goats following treatment.

Analyte Species; Breed Age; # of Animals Tolerance/ MRL Analytical Method LOD LOQ Route of Admini-stration Dose & Active Ingredient # of Doses Matrix Last Sampling Time Point (Post-Last Treatment) When Residues WERE Detected Sampling Time Point When NO Residues Were Detected (Post-Last Treatment) * Health Status Additional Information Source/Year
Erythro-mycin Goat; dairy type; 2–7 years; n = 10 US Tol: Not established. EMA MRL by extension from bovine to all food producing species: 40 ppb (milk). Bioassay NS NS IMM 300 mg Erythromycin at 12 h intervals 3 Milk 24 h (0.05 ppm §) 36 h Healthy Early & mid-lactation; Milked 2x/day, Whole tube per gland [60] 1984
Erythro-mycin Goat; NS; adult; n = 6 US Tol: Not established. EMA MRL by extension from bovine to all food producing species: 40 ppb (milk). Bioassay NS 0.024 ppm IV 10 mg/kg Erythromycin 1 Milk 12 h (0.14 ppm §) >12 h Healthy Early lactation [121] 2007
IM 15 mg/kg Erythromycin 1 Milk 12 h (0.24 ppm §) >12 h
Erythro-mycin Sheep; NS; 3–4 years; n = 6 US Tol: Not established. EMA MRL by extension from bovine to all food producing species: 40 ppb (milk). Bioassay NS 0.039 ppm IV 10 mg/kg Erythromycin 1 Milk 12 h (0.14 ppm §) 24 h Healthy Lactating [111] 2007
IM 10 mg/kg Erythromycin 1 Milk 12 h (0.16 ppm §) 24 h
SC 10 mg/kg Erythromycin 1 Milk 24 h (0.05 ppm §) >24 h
Erythro-mycin Sheep; NS; NS; n = 20 study; n = 4/time pt US Tol: Not established. EMA established MRL: 200 ppb (liver, kidney, muscle, fat). Bioassay NS Liver: 250 ppb IM 10 mg/kg Erythromycin daily 5 Liver 1 day (1.22 ppm) 3 days Healthy NS [110] 2000
Kidney: 250 ppb Kidney 1 days (0.77 ppm) 3 days
Muscle: 200 ppb Muscle 1 day (0.42 ppm) 3 days
Fat: 200 ppb Fat ND 1 day
Inj. Site: 200 ppb Inj. Site 15 days (0.37 ppm) >15 days
LS-MC NS 100 ppb IM 10 mg/kg Erythromycin daily 5 Liver 1 days (0.41 ppm) 3 days Healthy
Kidney 1 days (0.59 ppm) 3 days
Muscle 1 days (0.27 ppm) 3 days
Fat ND 1 day
Inj. Site 6 days (0.46 ppm) 9 days
Gamithro-mycin Sheep; Merino; 5–6 months; n = 9 study; n = 3/time pt US Tol: Not established. EMA MRL: Not established. LS-MC NS 10 ppb SC 6 mg/kg Gamithromycin 1 Skin 10 days (276 ppb) >10 days Healthy NS [125] 2014
Gamithro-mycin Sheep; NS; 7 months; n = 35 study; n = 5/ time pt US Tol: Not established. EMA established MRL: 300 ppb (liver); 200 ppb (kidney); 50 ppb (muscle & fat). LS-MC NS NS SC 6 mg/kg Gamithromycin 1 Liver NS ‡ NS ‡ Healthy NS [126] 2016
Kidney NS ‡ NS ‡
Muscle NS ‡ NS ‡
Fat NS ‡ NS ‡
Inj. Site NS ‡ NS ‡
Spiramycin Sheep; Awassi; adult; n = 1 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IV 20 mg/kg Spiramycin adipate 1 Milk 60 h (2.78 ppm §) >96 h Healthy Lactating; Milked 2×/day [24] 1973
Radio-activity NS NS IV 20 mg/kg Spiramycin (radiolabeled) 1 Milk 60 h (3.61 ppm §) >96 h
Spiramycin Sheep; Awassi; Adult; n = 2 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IM 20 mg/kg Spiramycin adipate 1 Milk 56 h (2.40 ppm §) >56 h Healthy Lactating; Milked 2x/day [29] 1974
Radio-activity NS NS Milk 56 h (3.61 ppm §) >56 h
Bioassay NS NS IM 20 mg/kg Spiramycin (radiolabeled) 1 Milk 56 h (1.79 ppm §) >56 h Diseased- mastitis
Radio-activity NS NS Milk 56 h (1.92 ppm §) >56 h
Tilmicosin Goats; NS; 2.5–3 years; n = 5 US Tol: Not established. EMA MRL by extension from ovine to all food producing species: 40 ppb (milk). Bioassay 10 ppb NS SC 10 mg/kg Tilmicosin 1 Milk 11 days (0.16 ppm §) 12 days Healthy Early lactation [112] 1997
Tilmicosin Sheep; Barki; 2–3 years; n = 5 US Tol: Not established. EMA established MRL: 40 ppb (milk). Bioassay NS 0.1 ppm SC 10 mg/kg Tilmicosin phosphate 1 Milk 8 days (0.04 ppm §) >8 days Healthy Mid-lactation [127] 1999
Tilmicosin Sheep; Suffolk crossbred; adult; n = 4 US Tol: Not established. EMA established MRL: 40 ppb (milk). HPLC 50 ppb NS SC 10 mg/kg Tilmicosin 1 Milk 11 days (46 ppb) >11 days NS Early & mid-lactation; Milked 2x/day [128] 1994
Tilmicosin Sheep; Beulah Cross; 10–11 weeks; n = 14 study (slaughter 4 time pts) US Tol: 1200 ppb (liver); 100 ppb (muscle). EMA established MRL: 1000 ppb (liver & kidney); 50 ppb (muscle & fat). Radio-activity NS NS SC 20 mg/kg Tilmicosin phosphate (radiolabeled) 1 Liver 28 days (2.7 ppm) >28 days Healthy NS [129] 2002
Kidney 28 days (0.55 ppm) >28 days
Muscle 28 days (1.35 ppm) >28 days
Fat 28 days (0.26 ppm) >28 days
Inj. Site 28 days (6.51 ppm) >28 days
NS; NS; n = 16 & 4 slaughter time pts HPLC 50 ppb NS SC 20 mg/kg Tilmicosin phosphate 1 Liver 28 days (160 ppb) >28 days Healthy
Kidney 28 days (73 ppb) >28 days
Muscle 7 days (193.5 ppb) 21 days
Fat 3 days (73 ppb) 7 days
Inj. Site 28 days (121.8 ppb) >28 days
Scottish Blackface; 6 months; n = 24 study; n = 4/time pt HPLC NS 50 ppb SC 30 mg/kg Tilmicosin phosphate 1 Liver 56 days (81 ppb) >56 days Healthy
Kidney 42 days (51 ppb) 56 days
Muscle 14 days
Fat 14 days
Inj. Site 56 days (81 ppb) >56 days
Swaledale; NS; n = 28 study; n = 4/tme pt HPLC NS 50 ppb SC 10 mg/kg Tilmicosin phosphate 1 Liver 35 days (59 ppb) 42 days Healthy
Kidney 21 days (73 ppb) 28 days
Muscle 14 days
Fat 14 days
Inj. Site 28 days (80 ppb) 35 days
Tilmicosin Sheep; NS; lambs; n = 12 study; n = 3/time pt US Tol: 1200 ppb (liver); 100 ppb (muscle). EMA established MRL: 50 ppb (muscle & fat); 1000 ppb (liver & kidney). Radio-activity NS NS SC 20 mg/kg Tilmicosin phosphate (radiolabeled) 1 Liver 28 days (2.7 ppm) >28 days Healthy NS [113] 1997
Kidney 28 days (0.55 ppm) >28 days
Muscle 28 days(<0.26 ppm) >28 days
Fat 28 days (<1.2 ppm) >28 days
NS; lambs; n = 12 study; n = 3/time pt Inj. Site 28 days (1.32 ppm) >28 days
HPLC NS 0.05 ppm SC 20 mg/kg Tilmicosin phosphate 1 Liver 28 days (0.16 ppm) >28 days Healthy NS
Kidney 28 days (0.06 ppm) >28 days
Muscle 7 days (0.19 ppm) 21 days
Swaledale; NS; n = 28 study; n = 4/time pt Fat 7 days (<0.05 ppm) 7 days
Inj. Site 28 days (0.12 ppm) >28 days
LC NS 0.05 ppm SC 10 mg/kg Tilmicosin phosphate 1 Liver 21 days (0.07 ppm) 28 days Healthy NS
Kidney 21 days (0.07 ppm) 28 days
NS; adult; n = 4 Muscle ND @ 14 days 14 days
Fat 14 days
Inj. Site 28 days (0.08 ppm) 35 days
HPLC NS 0.05 ppm SC 10 mg/kg Tilmicosin phosphate 1 Milk 10 days (0.06 ppm) 14 days Healthy Lactating
Tilmicosin Sheep; Suffolk crossbred; Adult; n = 4 US Tol: Not established. EMA established MRL: 50 ppb (milk). HPLC NS 50 ppb SC 10 mg/kg Tilmicosin 1 Milk 15 days (0.3 ppm §) >15 days Healthy Early lactation [114] 2008
Tulathro-mycin Goats; Boer; 5–7 months; n = 16 study; n = 4/time pt US Tol: Not established. EMA established MRL: 450 ppb (muscle); 250 ppb (fat); 5400 ppb (liver);1800 ppb (kidney). UPLC 0.7 ppb 2 ppb SC 2.5 mg/kg Tulathromycin at 7-day interval 2 Liver 20 days (0.78 ppm)) >20 days Healthy NS [123] 2012
Kidney 20 days (0.44 ppm) >20 days
Muscle 5 days (0.46 ppm) 10 days
Fat 10 days (0.17 ppm) 20 days
Tulathro-mycin Goats; Mixed; 7–8 weeks; n = 6 US Tol: Not established. EMA established MRL: 450 ppb (muscle); 250 ppb (fat); 5400 ppb (liver); 1800 ppb (kidney). LC-MS Liver: 0.75 ppm Liver: 1.91 ppm SC 2.5 mg/kg Tulathromycin 1 Liver 14 days Healthy Juveniles NS [124] 2012
Kidney 14 days
Kidney: 0.29 ppm Kidney: 1.66 ppm Muscle < 14 days
Fat 14 days
Muscle: 0.24 ppm Muscle: 0.69 ppm Inj. Site 35 days (0.25 ppm) >35 days
Mixed; 5–6 months; n = 30 stdy; n = 6/time pt SC 2.5 mg/kg Tulathromycin 1 Liver 12 days (1.18 ppm) 18 days Healthy Market-age
Fat: 0.14 ppm Fat: 0.61 ppm Kidney 48 days (0.31 ppm) >48 days
Muscle 5 days (0.24 ppm) 12 days
Inj. Site: 0.24 ppm Inj. Site: 0.69 ppm Fat 12 days (0.15 ppm) 18 days
Inj. Site 18 days (1.27 ppm) 27 days
Mixed; 2–3 weeks; n = 12 SC 2.5 mg/kg Tulathromycin at 7-day interval 3 Liver 7 days (0.7 ppm) >7 days Healthy Juveniles
Kidney >7 days
Muscle >7 days
Fat >7 days
Inj. Site 7 days (8.76 ppm) >7 days
SC 7.5 mg/kg Tulathromycin at 7-day interval 3 Liver 7 days (3.4 ppm) >7 days Healthy Juveniles
Kidney 7 days (1.65 ppm) >7 days
Muscle 7 days (0.65 ppm) >7 days
Fat 7 days (0.36 ppm) >7 days
Inj. Site 7 days (17.9 ppm) >7 days
SC 12.5 mg/kg Tulathromycin at 7-day interval 3 Liver 7 days (4.87 ppm) >7 days Healthy Juveniles
Kidney 7 days (3.28 ppm) >7 days
Muscle 7 days (1.33 ppm) >7 days
Fat 7 days (0.65 ppm) >7 days
Inj. Site 7 days (24.4 ppm) >7 days
Tulathro-mycin Goats; dairy type; 2–5 years; n = 8 US Tol: Not established. EMA MRL: Not established. HPLC 1.8 ppb 5.0 ppb SC 2.5 mg/kg Tulathromycin 1 Milk 45 days (2 ppb) >45 days Healthy, Lactating; Milked 2×/day [115] 2016
Tulathro-mycin Goats; NS; 30–36 months; n = 5 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IV 2.5 mg/kg Tulathromycin 1 Milk 19 days (0.08 ppm §) >19 days Healthy Lactating [116] 2012
IM 2.5 mg/kg Tulathromycin 1 Milk 19 days (0.1 ppm §) >19 days
Tulathro-mycin Goats; dairy type; 1–7 years; n = 8 US Tol: Not established. EMA MRL: Not established. LS-MS 1.8 ppb 5.0 ppb SC 2.5 mg/kg Tulathromycin at 7-day interval 2 Milk 58 days (0.5 ppb) 61 days Healthy Lactating; Milked 2×/day [117] 2016
Tulathro-mycin Sheep; NS; NS; n = 30 study; n = 3/time pt US Tol: Not established. EMA established MRL: 450 ppb (muscle); 250 ppb (fat); 5400 ppb (liver); 1800 ppb (kidney). LS-MC NS Liver: 300 ppb IM 2.5 mg/kg Tulathromycin 1 Liver 35 days (0.3 ppm) 42 days Healthy NS [130] 2015
Kidney: 200 ppb Kidney 21 days (0.2 ppm) 28 days
Muscle; 50 ppb Muscle 21 days (0.05 ppm) 28 days
Fat: 50 ppb Fat 14 days (0.05 ppm) 21 days
Inj. Site: 50 ppb Inj. Site 49 days (0.15 ppm) >49 days
Tylosin Goats; NS; adult; n = 5 US Tol: Not established. EMA MRL by extension from bovine to all food producing species: 50 ppb (milk). Bioassay NS NS IV 15 mg/kg Tylosin tartrate 1 Milk 24 h (0.6 ppm) >24 h Healthy Lactating [118] 1991
IM 15 mg/kg Tylosin tartrate 1 Milk 24 h (1.7 ppm) >24 h
Tylosin Sheep; Awassi; adult; n = 3 US Tol: Not established. EMA MRL by extension from bovine to all food producing species: 50 ppb (milk). Bioassay NS NS IM 20 mg/kg Tylosin 1 Milk 26 h (1.80 ppm) >26 h Healthy Lactating; Milked 2x/day [119] 1973
Milk 26 h (0.67 ppm) >26 h Diseased- mastitis
Tylosin Sheep; Merino; adult; n = 7 US Tol: Not established. EMA MRL by extension from bovine to all food producing species: 50 ppb (milk). HPLC NS NS IM 10 mg/kg Tylosin 5 Milk 36 h (30.9 ppb) 48 h Healthy Lactating; Milked 2×/day [120] 2001

§ Data points manually extracted use scanning software (Webplot digitizer or UnScanIt 7.0). # = number. ‡ Liver HL reported= 5.48 days; Kidney HL reported = 4.22 days; Muscle HL = 2.55 days; Fat HL reported = 2.82 days; Injection site core = 4.43 days; Injection site ring = 2.39 days. * Projected time for which residues could still be detected based on study protocol for sample collection time points and sample concentration results. Authors caution readers to critically evaluate these publications to estimate when full residue depletion might occur. Abbreviations: 2×/day: twice daily. LOD: Limit of detection. LOQ: Limit of quantification. EMA: European Medicines Agency. MRL: Maximum residue limit. ND: Not detected. NS: Not specified. Routes of Administration: IMM = intramammary, IM = intramuscular, IV = intravenous, SC = subcutaneous. Units: s = seconds, min = minutes, h = hours, ppb = parts per billion, ppm = parts per million.

Sulfonamide residues in milk or edible tissue samples from sheep or goats following treatment.

Analyte Species; Breed; Age; # of Animals Tolerance/MRL Analytical Method LOD LOQ Route of Admini-stration Dose & Active Ingredient # of Doses Matrix Last Sampling Time Point (Post-Last Treatment) When Residues WERE Detected Sampling Time Point When NO Residues Were Detected (Post-Last Treatment) * Health Status Additional Information Source/Year
Sulfa-dimethoxine Goat; NS; adult; n = 5 US Tol: Not established. EMA MRL: Not established. Color-imetrically NS NS PO 286 mg/kg sulfadimethoxine 1 Milk 2 days (NS) 3 days Healthy Lactating [135] 2016
Sulfa-nilamide Goat; NS; Adult; n = 1 US Tol: Not established. EMA established MRL: 100 ppb (milk). Spectro-metric NS NS IMM 1000 mg Sulfanilamide 1 Milk 4 days (143 ppm) >4 days Healthy Lactating; Single gland [132] 1958
Sulfa-cetamide Goat; NS; Adult; n = 1 US Tol: Not established. EMA established MRL: 100 ppb (milk). Spectro-metric NS NS IMM 1000 mg Sulfacetamide 1 Milk 4 days (2520 ppm) >4 days Healthy Lactating; Single gland [132] 1958
Sulfa-nilamide Sheep; NS; adult; n = 7 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IV; PO 150 mg/kg Sulfanilamide IV once then 100 mg/kg sulfanilamide PO at 12 h intervals 8 Liver 8 days (79 ppm) >8 days Healthy NS [136] 1977
Kidney 8 days (119 ppm) >8 days
Muscle 8 days (50 ppm) >8 days
Sulfa-methoxy-pyridazine Sheep; NS; adult; n = 7 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS PO 35 mg/kg Sulfamethoxy-pyridazine once then 25 mg/kg Sulfamethoxy-pyridazine daily 4 Liver 8 days (55 ppb) >8 days Healthy NS [136] 1977
Kidney 8 days (115 ppb) >8 days
Muscle 8 days (41 ppb) >8 days
Sulf-athiazole Sheep; mixed; lambs; n = 15 study; n = 3/time pt US Tol: Not established. EMA MRL: Not established. Spectrometric NS NS IV 72 mg/kg Sodium sulfathiazole 1 Liver 1 day (0.12 ppm §) >1 day Healthy NS [137] 1977
Kidney 1 days (0.11 ppm §) >1 day
Muscle 16 h (0.27 ppm §) 1 day
Fat 16 h (0.26 ppm §) 1 day
Sulfa-merazine Sheep; mixed; 22 months; n = 13 study; n = 3/time pt US Tol: Not established. EMA MRL: Not established. HPLC NS 0.1 ppm PO 132 mg/kg Sulfamerazine once, then 66 mg/kg at 12 h intervals 6 Liver 5 days (0.11 ppm) 7 days Healthy NS [138] 1972
Kidney 5 days (0.07 ppm) 7 days
Muscle 7 days (0.12 ppm) 10 days
Fat 7 days (0.05 ppm) >7 days
Sulfa-merazine Sheep; NS; adult; n = 12 US Tol: Not established. EMA established MRL: 100 ppb (milk). Spectro-metric NS NS PO 100 mg/kg Sulfamerazine 1 Milk 2 days (3.7 ppm) >2 days Healthy Lactating; Full dose/ gland [139] 1978
IV 100 mg/kg Sulfamerazine 1 Milk 1 day (5.0 ppm) 2 days
IM 100 mg/kg Sulfamerazine 1 Milk 1 days (4.2 ppm) 2 days
IMM 500 mg Sulfamerazine 1 Milk 12 min (428 ppm) >12 min
Sulfa-methazine † Goat; West African Dwarf; 1 year; n = 20 study; n = 1/time point US Tol: Not established. EMA MRL: Not established. Spectro-metric 0.05 ppm NS IM 100 mg/kg Sulfadimidine 1 Liver 30 days (5.29 ppm) >30 days Healthy NS [133] 2018
Kidney 30 days (3.84 ppm) >30 days
Muscle 30 days (2.01 ppm) >30 days
Fat 30 days (4.84 ppm) >30 days
IM 100 mg/kg Sulfadimidine co-admin w/5 mg/kg piroxicam 1 Liver 30 days (5.33 ppm) >30 days
Kidney 30 days (4.79 ppm) >30 days
Muscle 30 days (1.38 ppm) >30 days
Fat 30 days (4.53 ppm) >30 days
Sulfa-methazine † Sheep; Targhee/Rambouillet; lambs; n = 16 study; n = 2/time pt US Tol: Not established. EMA MRL: Not established. Spectro-metric NS NS IV 107.25 mg/kg Sodium sulfamethazine 1 Liver 4 days (0.11 ppm) >4 days Healthy NS [134] 1977
Kidney 4 days (0.14 ppm) >4 days
Muscle 4 days (0.09 ppm) >4 days
Fat 4 days (0.05 ppm) >4 days
Sulfa-methazine † Sheep; crossbred; 2–3 years; n = 25 study; n = 5/time pt US Tol: Not established. EMA MRL: Not established. HPLC NS 0.1 ppm PO 391 mg/kg Sulfamethazine 1 Liver 4 days (0.3 ppm) 8 days Healthy NS [140] 1991
Kidney 4 days (0.25 ppm) 8 days
Muscle 4 days (0.2 ppm) 8 days
Fat ND 4 days
Sulfa-methazine † Sheep; crossbred; adult; n = 10 US Tol: Not established. EMA Established MRL: 100 ppb (milk). Spectro-metric NS NS PO 15,000 mg Sulfamethazine 1 Milk 1 day (NS) >1 day Healthy Lactating [131] 1965
PO 15,000 mg Sulfamethazine at 12 h interval 2 Milk 2 days (NS) >2 days Healthy
PO 15,000 mg Sulfamethazine at 16 h interval 2 Milk 2 days (NS) >2 days Healthy
PO 15,000 mg Sulfamethazine at 22 h interval 2 Milk 2 days (NS) >2 days Healthy
PO 15,000 mg Sulfamethazine at 24 h interval 2 Milk 2 days (NS) >2 days Healthy
PO 15,000 mg Sulfamethazine at 25 h interval 2 Milk 53 h (NS) >53 h Diseased- mastitis
PO 15,000 mg Sulfamethazine first dose, 10,000 mg second dose at 24 h interval 2 Milk 2 days (NS) >2 days Healthy
PO 15,000 mg Sulfamethazine first dose, 7000 mg second dose at 24 h interval 3 Milk 2 days (NS) >2 days Healthy
PO 15,000 mg Sulfamethazine first dose, 7000 mg second dose at 22 h interval 3 Milk 78 h (NS) >78 h Diseased- mastitis
PO 15,000 mg Sulfamethazine first 2 doses at 13 h interval, 7000 mg third dose at 23 h interval 3 Milk 74 h (NS) >74 h Diseased- mastitis
PO 15,000 mg Sulfamethazine first 2 doses at 13 h interval, 7000 mg third dose at 22 h interval 3 Milk 83 h (NS) >83 h Diseased- mastitis
PO 18,000 mg first dose, 6000 mg second dose at 17 h interval then 19 h interval 3 Milk 80 h (NS) >80 h Diseased- mastitis
PO 18,000 mg Sulfamethazine first dose, 6000 mg at 24 h intervals 4 Milk 96 h (NS) >96 h Diseased- mastitis
Sulfa-methazine † Sheep; NS; NS; NS US Tol: Not established. EMA MRL: Not established. NS NS NS PO 107.25 mg/kg Sulfamethazine 1 Liver 2 days (0.1 ppm §) >2 days Healthy NS [141] 1978
Kidney 2 days (0.23 ppm §) >2 days
Muscle 2 days (0.15 ppm §) >2 days
Fat 36 h (0.16 ppm §) 2 days
Sulfa-methazine † Sheep; Suffolk; NS; n = 2; n = 1/time pt US Tol: Not established. EMA MRL: Not established. Radioactivity NS NS PO 100 mg/kg Sulfamethazine (radiolabeled) 1 Liver 2 days (10 ppm) >2 days Healthy NS [142] 1983
Kidney 2 days (22 ppm) >2 days
Muscle 2 days (3 ppm) >2 days
Sulfa-methazine † Sheep; Balady; 2–4 years; n = 9 study; n = 3/time pt US Tol: Not established. EMA MRL: Not established. NS NS NS IM 0.1 mg/kg Sulfadimidine 1 Liver 4 h (20 ppm) >4 h Healthy NS [143] 1980
Kidney 4 h (198 ppm) >4 h
Muscle 4 h (11 ppm) >4 h
Sulfadiazine Sheep; Balady; 2–4 years; n = 9 study; n = 3/time pt US Tol: Not established. EMA MRL: Not established. NS NS NS IM 0.1 mg/kg Sulfadiazine 1 Liver 4 h (25 ppm) >4 h Healthy NS [143] 1980
Kidney 4 h (40 ppm) >4 h
Muscle 4 h (13 ppm) >4 h

§ Data points manually extracted use scanning software (Webplot digitizer or UnScanIt 7.0). # Number. † Sulfamethazine and sulfadimidine are the same chemical/active ingredient. * Projected time for which residues could still be detected based on study protocol for sample collection time points and sample concentration results. Authors caution readers to critically evaluate these publications to estimate when full residue depletion might occur. Abbreviations: LOD: Limit of detection. LOQ: Limit of quantification. EMA: European Medicines Agency. MRL: Maximum residue limit. NS: Not specified. Routes of Administration: IMM = intramammary, IM = intramuscular, IV = intravenous, PO = per os. Units: s = seconds, min = minutes, h = hours, ppb = parts per billion, ppm = parts per million.

Tetracycline residues in milk or edible tissue samples from sheep or goats following treatment.

Analyte Species;Breed; Age; # of Animals Tolerance/MRL Analytical Method LOD LOQ Route of Admini-stration Dose & Active Ingredient # of Doses Matrix Last Sampling Time Point (Post-Last Treatmnet) When Residues WERE Detected Sampling Time Point When NO Residues Were Detected (Post-Last Treatment) * Health Status Additional Information Source/Year
Chlortetra-cycline Sheep; Chios & Friesian; adult; n = 4 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). Bioassay NS NS IM 25 mg/kg Chlor-tetracycline hydrochloride 1 Milk 72 h (0.1 ppm) 120 h (R udder) (0.28 ppm) >72 h >120 h (R udder) Healthy Lactating; Only right ½ of udder infused. [147] 1982
IMM 426 mg Chlor-tetracycline hydrochloride in right half of udder. 1 Milk 38 h (L udder) (0.09 ppm) 48 h (L udder)
Chlortetra-cycline Sheep; NS; lambs; NS US Tol: 6000 ppb (liver); 12,000 ppb (kidney, fat); 2000 ppb (muscle). EMA established MRL for all food producing species: 300 ppb (liver); 600 ppb (kidney); 100 ppb (muscle). NS NS Liver: 0.03 ppm POMF 50 mg/kg Chlor-tetracycline daily 42 Liver 0 days (0.11 ppm) 2 days Healthy NS [148] 1996
Kidney: 0.028 ppm Kidney 2 days (0.06 ppm) 4 days
Muscle: 0.027 ppm Muscle 0 days (0.03 ppm) 2 days
Fat: 0.025 ppm Fat ND 0 days
Chlortetra-cycline Sheep; NS; lambs; NS US Tol: 6000 ppb (liver); 12,000 ppb (kidney, fat); 2000 ppb (muscle). EMA established MRL for all food producing species: 300 ppb (liver); 600 ppb (kidney); 100 ppb (muscle). NS NS Liver: 0.03 ppm POMF 50 mg/kg Chlor-tetracycline co-admin with 50 mg/kg sulfamethazine daily 42 Liver 0 days (0.21 ppm) 4 days Healthy NS [148] 1996
Kidney: 0.028 ppm Kidney 6 days (0.05 ppm) 8 days
Muscle: 0.027 ppm Muscle 0 days (0.04 ppm) 4 days
Fat: 0.025 ppm Fat ND 0 days
Doxy-cycline Goat; NS; adult; n = 6 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IV 5 mg/kg Doxycycline hydrochloride 1 Milk 48 h (0.12 ppm §) >2 days Healthy Lactating [149] 1989
Mino-cycline Goat; NS; 1.5–2 years; n = 6 US Tol: Not established. EMA MRL: Not established. Bioassay NS NS IV 5 mg/kg Minocycline hydrochloride 1 Milk 36 h (0.11 ppm) 2 days Healthy Lactating [150] 1999
Oxytetra-cycline Sheep; Chios & Friesian; adult; n = 4 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). Bioassay NS NS IM 30 mg Oxytetracycline hydrochloride 1 Milk 38 h (0.7 ppm) 48 h Healthy Lactating; Only right ½ of udder infused. [147] 1982
IMM 420 mg Oxytetracycline hydrochloride in right half of udder 1 Milk 110 h (R udder) (0.58 ppm) 120 h (R udder)
14 h (L udder) (1.22 ppm 24 h (L udder)
Oxytetra-cycline Sheep; Awassi; adult; n = 8 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). Bioassay 0.5 ppm NS IM 20 mg/kg Oxytetracycline 1 Milk 72 h (NS) >3 days Healthy Early lactation [151] 1982
Oxytetra-cycline Sheep; mixed breed; NS; n = 24 study; n = 4/time pt US Tol: 6000 ppb (liver); 12,000 ppb (kidney, fat); 2000 ppb (muscle). EMA established MRL for all food producing species: 300 ppb (liver); 600 ppb (kidney); 100 ppb (muscle). HPLC NS Liver: 85 ppb IM 19.8 mg/kg Oxytetracycline (long acting) 1 Liver NS 14 days NS NS [152] 1997
Kidney: 42 ppb Kidney NS 14 days
Muscle: 45 ppb Muscle NS 14 days
Fat: 45 ppb Fat NS 14 days
Inj. Site NS 14 days
Oxytetra-cycline Sheep; Sardinian; adult; n = 5 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). HPLC 5.2 ppb 17.5 ppb IMM 20 mg/kg Oxytetracycline 1 Milk 7 days (0.1 ppm §) >7 days NS Lactating; Milked 2×/day [153] 1999
IM 20 mg/kg Oxytetracycline 1 Milk 7 days (4.15 ppm §) >7 days
Oxytetra-cycline Sheep; mixed breed; NS; n = 24 study; n = 4/time pt US Tol: 6000 ppb (liver);12,000 ppb (kidney, fat); 2000 ppb (muscle). EMA established MRL for all food producing species: 300 ppb (liver); 600 ppb (kidney); 100 ppb (muscle). HPLC NS Liver: 85 ppb IM 20 mg/kg Oxytetracycline (long acting) 1 Liver 7 days (52 ppb) 14 days Healthy NS [154] 2000
Kidney: 42 ppb Kidney 14 days (65 ppb) >14 days
Muscle: 45 ppb; Muscle 7 days (49 ppb) 14 days
Fat: 45 ppb Fat 7 days (88 ppb) 14 days
Inj. Site 14 days (59 pb) >14 days
Oxytetra-cycline Sheep; NS; 16 months; n = 2 study; n = 1/ time pt US Tol: 6000 ppb (liver); 12,000 ppb (kidney, fat); 2000 ppb (muscle). EMA established MRL for all food producing species: 300 ppb (liver); 600 ppb (kidney); 100 ppb (muscle). LC-MS Liver Oxy: 15.3 ppb Liver Oxy: 50 ppb IM 10 mg/kg Oxytetracycline daily 5 Liver Oxy: 2 days (272.8 ppb) Oxy: >2 days Healthy NS [155] 2008
Liver 4-Epi †: 16.6 ppb Liver 4-Epi †: 50 ppb 4-Epi †: 4 h (217.8 ppb) 4-Epi †: 2 days
Kidney Oxy: 15.7 ppb Kidney Oxy: 50 ppb Kidney Oxy: 2 days (1342.4 ppb) Oxy: >2 days
Kidney 4-Epi †: 17.5 ppb Kidney 4-Epi †: 50 ppb 4-Epi †: 2 days (55 ppb) 4-Epi †: >2 days
Muscle Oxy: 12.4 ppb Muscle Oxy: 50 ppb Muscle Oxy: 2 days (73.6 ppb) Oxy: >2 days
4-epi-Oxytetra-cycline Muscle 4-Epi †: 13.9 ppb Muscle 4-Epi †: 30 ppb 4-Epi †: 4 h (34.2 ppb) 4-Epi †: 2 days
Fat Oxy: 12.4 ppb Fat Oxy: 50 ppb Fat Oxy: 4 h (3610.7 ppb) Oxy: 2 days
Fat 4-Epi †: 14.1 ppb Fat 4-Epi †: 30 ppb 4-Epi †: 4-Epi †: 4 h
Inj. Site Oxy: 12.4 ppb Inj. Site Oxy: 30 ppb Inj. Site Oxy: 2 days (763.2 ppb) Oxy: >2 days
Inj. Site 4-Epi †: 13.9 ppb Inj. Site 4-Epi †: 30 ppb 4-Epi†: 2 days (34.5 ppb) 4-Epi †: >2 days
Oxytetra-cycline Sheep; Chios; 3 years; n = 20 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). LC-MS NS 20 ppb IM 10 mg/kg Oxytetracycline daily 5 Milk 7 days (33.2 ppb) 8 days Healthy Lactating; Milked 2×/day [156] 2008
Oxytetra-cycline Sheep; Comisana; adult; n = 8 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). HPLC NS NS IM 20 mg/kg Oxytetracycline (long acting) 1 Milk 7.5 days (50 ppb) 8 days Healthy Lactating; Milked 2×/day [157] 2000
Oxytetra-cycline Sheep; desert; 9–12 months; n = 12/ study; n = 4/time pt US Tol: 6000 ppb (liver);12,000 ppb (kidney, fat); 2000 ppb (muscle). EMA establsihed MRL for all food producing species: 300 ppb (liver); 600 ppb (kidney); 100 ppb (muscle). Bioassay NS NS IM 5000 mg/kg Oxytetracycline (long acting) daily 5 Liver 10 days (1.51 ppm) >10 days NS NS [158] 2007
Kidney 10 days (6.7 ppm) >10 days
Muscle 10 days (70.87 ppm) >10 days
Inj. Site 10 days (1227.7 ppm) >10 days
Oxytetra-cycline Sheep; Chios; 16 months; n = 30 study; n = 5/time pt US Tol: 6000 ppb (liver); 12,000 ppb (kidney, fat); 2000 ppb (muscle). EMA established MRL for all food producing species: 300 ppb (liver); 600 ppb (kidney); 100 ppb (muscle). LC-MS NS Liver: 50 ppb IM 10 mg/kg Oxytetracycline daily 5 Liver Oxy: 6 days (0.05 ppm) Oxy: 9 days Healthy NS [146] 2009
4-Epi †: 2 days (0.05 ppm) 4-Epi †: 4 days
Kidney: 50 ppb Kidney Oxy: 9 days (0.08 ppm) Oxy: 12 days
4-Epi †: 4 days (0.05 ppm) 4-Epi †: 6 days
Muscle: 30 ppb Muscle Oxy: 4 days (0.04 ppm) Oxy: 6 days
4-epi-Oxytetra-cycline 4-Epi †: 2 days (0.04 ppm) 4-Epi †: 4 days
Fat: 30 ppb Fat Oxy: 0 days (2.7 ppm) Oxy: 2 days
4-Epi †: 4-Epi †: 0 days
Inj. Site: 30 ppb Inj. Site Oxy: 9 days (0.04 ppm) Oxy: 12 days
4-Epi †: 2 days (0.062 ppm) 4-Epi †: 4 days
Oxytetra-cycline Goat; Saanen; adult; n = 8 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). HPLC NS NS IM 20 mg/kg Oxytetracycline (long acting) 1 Milk 7.5 days (60 ppb) 8 days Healthy Lactating; Milked 2×/day [157] 2000
Oxytetra-cycline Goat; mixed breed; NS; n = 32 Mixed breed; adult; n = 10 US Tol: 6000 ppb (liver); 12,000 ppb (kidney, fat); 2000 ppb (muscle); Not approved (milk). EMA established MRL for all food producing species: 300 ppb (liver); 600 ppb (kidney); 100 ppb (muscle); 100 ppb (milk). Bioassay 0.1 ppm NS IM 20 mg/kg Oxytetracycline (long acting) 1 Liver 7 days (385 ppb) 14 days Healthy Lactating; Milked 2×/day [145] 2002
Kidney 7 days (376 ppb) 14 days
Muscle 7 days (246 ppb) 14 days
Fat 96 h (236 ppb) 7 days
Inj. Site 14 days (1129 ppb) >14 days
HPLC 0.15 ppm IM 20 mg/kg Oxytetracycline (long acting) 1 Milk 178 h (0.03 ppm) >178 h Healthy Lactating; Milked 2×/day
SC 20 mg/kg Oxytetracycline (long acting) 1 Milk 178 h (0.05 ppm) >178 h
Oxytetra-cycline Goat; Saanen; adult; n = 8 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). Bioassay 0.25 ppm NS IMM 426 mg Oxytetracycline per half daily 3 Milk 5 h (0.50 ppm §) >5 h Healthy Lactating; Milked 2×/day [53] 1984
Oxytetra-cycline Goat; NS; adult; NS US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). HPLC NS NS IM 15 mg/kg Oxytetracycline daily 4 Milk 100 h (0.46 ppm) >100 h Healthy Lactating [159] 1994
Oxytetra-cycline Goat; Canary Island; adult; n = 5 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). HPLC NS NS IM 15 mg/kg Oxytetracycline 4 Milk 96 h (0.46 ppm) >96 h Healthy Lactating; Milked 2×/day [160] 1995
Oxytetra-cycline Goat; Saanen; adult; n = 8 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). LC-MS 15 ppb 50 ppb IM 20 mg/kg Oxytetracycline 1 Milk 180 h (60 ppb) 8 days Healthy Lactating; Milked 2×/day [161] 2002
Oxytetra-cycline Goat; Nubian, Alpine & LaMancha; adult; n = 15 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). HPLC NS NS IM 17.6 mg/kg Oxytetracycline at 48 h interval 2 Milk 96 h (87 ppb) >96 h Healthy Mid-lactation; Milked 2×/day [144] 2015
Oxytetra-cycline Goat; Murciano-Granadina; adult; n = 5 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). HPLC NS NS IV 20 mg/kg Oxytetracycline chlorhydrate 1 Milk 2 days (0.25 ppm §) >2 days Healthy Lactating; Milked 1×/day [162] 2001
IM 20 mg/kg Oxytetracycline chlorhydrate 1 Milk 3 days (0.36 ppm §) >3 days
IM 20 mg/kg Oxytetracycline dehydrate (Long Acting) 1 Milk 3 days (0.27 ppm §) >3 days
Oxytetra-cycline Goat; NS; 2–7 years; n = 10 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). Bioassay NS NS IMM 426 mg Oxytetracycline hydrochloride per half at 12 h intervals 3 Milk 96 h (0.02 ppm §) 108 h Healthy Early & mid-lactation; Milked 2×/day; 1 tube/ mammary gland [60] 1984
Tetra-cycline Sheep; Awassi; Adult; n = 2 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). Bioassay NS NS IM 20 mg/kg Tetracycline 1 Milk 48 h (0.08 ppm §) >2 days Healthy Lactating; Milked 2×/day [29] 1974
48 h (0.04 ppm §) >2 days Diseased- mastitis
Radio-activity NS NS IM 20 mg/kg Tetracycline (radiolabeled) 1 Milk 48 h (0.14 ppm §) >2 days Healthy
48 h (0.2 ppm §) >2 days Diseased- mastitis
Tetra-cycline Sheep; Awassi; adult; n = 4 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). Bioassay NS NS IV 20 mg/kg Tetracycline hydrochloride (radiolabeled), then 5 mg/kg for 2 doses at 90 min interval 1 Milk 60 h (0.70 ppm §) 4 days Healthy Lactating; Milked 2×/day [24] 1973
Radio-activity NS NS 60 h (0.12 ppm §) 4 days
Tetra-cycline Goat; Canary Island; adult; n = 5 US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). HPLC NS NS IM 15 mg/kg Tetracycline 4 Milk 96 h (0.91 ppm) >96 h Healthy Lactating; Milked 2×/day [160] 1995
Tetra-cycline Goat; NS; adult; NS US Tol: Not established. EMA established MRL for all food producing species: 100 ppb (milk). HPLC NS NS IM 15 mg/kg Tetracycline daily 4 Milk 100 h (0.91 ppm) >100 h Healthy Lactating [159] 1994

§ Data points manually extracted use scanning software (Webplot digitizer or UnScanIt 7.0). # = number. † 4-epi-Oxytetracycline Metabolite. * Projected time for which residues could still be detected based on study protocol for sample collection time points and sample concentration results. Authors caution readers to critically evaluate these publications to estimate when full residue depletion might occur. Abbreviations: 2×/day: twice daily. LOD: Limit of detection. LOQ: Limit of quantification. EMA: European Medicines Agency. MRL: Maximum residue limit. ND: Not detected. NS: Not specified. Routes of Administration: IMM = intramammary, IM = intramuscular, IV = intravenous, PO = per os, POMF = per os as medicated feed, SC= subcutaneous. Units: s = seconds, min = minutes, h = hours, ppb = parts per billion, ppm = parts per million.

References

1. Akinmoladun, O.F.; Muchenje, V.; Fon, F.N.; Mpendulo, C.T. Small Ruminants: Farmers’ Hope in a World Threatened by Water Scarcity. Animals; 2019; 9, 456. [DOI: https://dx.doi.org/10.3390/ani9070456] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31323882]

2. Food and Agriculture Organization of the United Nations. FAOSTAT. 2022; Available online: https://www.fao.org/faostat/en/#compare (accessed on 22 November 2021).

3. Food and Drug Administration. Minor Use/Minor Species; Food and Drug Administration: Spring, MD, USA, 2022.

4. European Medicines Agency. Guideline on Safety and Residue Data Requirements for the Establishment of Maximum Residue Limits in Minor Species; European Medicines Agency: Amsterdam, The Netherlands, 2022.

5. Congress of the United States. Minor Use and Minor Species Animal Health Act of 2004; Congress of the United States: Washington, DC, USA, 2004.

6. Food and Drug Administration. Title 21, Chapter I, Subchapter E, Part 530: Extralabel Drug Use in Animals; Food and Drug Administration: Silver Spring, MD, USA, 2022.

7. Northcutt, J.K. Preslaughter factors affecting poultry meat quality. Poultry Meat Processing; Woodhead Publishing: Cambridge, UK, 2000.

8. World Health Organization. Critically Important Antimicrobials for Human Medicine 6th Revision; World Health Organization: Geneva, Switzerland, 2018.

9. Riviere, J.E.; Craigmill, A.L.; Sundlof, S.F. Aminoglycosides. Handbook of Comparative Pharmacokinetics and Residues of Veterinary Antimicrobials; CRC Press: Boca Raton, FL, USA, 1991.

10. European Medicines Agency Committee for Veterinary Medicinal Products. Apramycin Summary Report (2); European Medicines Agency Committee for Veterinary Medicinal Products: Amsterdam, The Netherlands, 1999; Volume 526, pp. 1-8.

11. Heitzman, R. Dihydrostreptomycin Streptomycin. Residues Some Vet. Drugs Anim. Foods; 1995; 41, pp. 17-29.

12. Brown, S.; Riviere, J.; Coppoc, G.; Hinsman, E.; Carlton, W.; Steckel, R. Single intravenous and multiple intramuscular dose pharmacokinetics and tissue residue profile of gentamicin in sheep. Am. J. Vet. Res.; 1985; 46, pp. 69-74. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/3970446]

13. Brown, S.; Coppoc, G.; Riviere, J. Effects of dose and duration of therapy on gentamicin tissue residues in sheep. Am. J. Vet. Res.; 1986; 47, pp. 2373-2379. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/3789497]

14. Brown, S.; Baird, A. Evaluation of renal gentamicin depletion kinetic properties in sheep, using serial percutaneous biopsies. Am. J. Vet. Res.; 1988; 49, pp. 2056-2059.

15. The Upjohn Company. NADA 011-315 Neomycin 325/Neomix Ag 325 Soluble Powder—Supplemental Approval (Date of Approval: 3 April 1996); FOI—Neomix- NADA 011-315 The Upjohn Company: Hastings, MI, USA, 1996; pp. 1-3.

16. European Medicines Agency Committee for Veterinary Medicinal Products. Neomycin Summary Report (2); EMEA/MRL/730/00-Final European Medicines Agency Committee for Veterinary Medicinal Products: Amsterdam, The Netherlands, 2000; Volume 730, pp. 1-8.

17. Livingston, R.C. Neomycin. Residues Some Vet. Drugs Anim. Foods; 1995; 41, pp. 57-67.

18. National Library of Medicine. Drugs and Lactation Database (LactMed); National Library of Medicine: Bethesda, MD, USA, 2006.

19. El-Sooud, K.A. Pharmacokinetics of amikacin in lactating goats. Zent. Vet. A; 1999; 46, pp. 239-246. [DOI: https://dx.doi.org/10.1046/j.1439-0442.1999.00212.x]

20. Agrawal, A.; Singh, S.; Jayachandran, C. Pharmacokinetics of amikacin in goats after single intramuscular administration. Indian J. Pharmacol.; 2001; 33, 374.

21. Haritova, A.; Lashev, L. Pharmacokinetics of amikacin in lactating sheep. Vet. Res. Commun.; 2004; 28, pp. 429-435. [DOI: https://dx.doi.org/10.1023/B:VERC.0000035023.05511.11]

22. Ziv, G.; Kurtz, B.; Risenberg, R.; Glickman, A. Serum and milk concentrations of apramycin in lactating cows, ewes and goats. J. Vet. Pharmacol. Ther.; 1995; 18, pp. 346-351. [DOI: https://dx.doi.org/10.1111/j.1365-2885.1995.tb00602.x]

23. El-Gendi, A.Y.; Amer, A.M.; Azooz, H.A. Disposition kinetics and milk residues of apramycin in goats. Proceedings of the European Association of Veterinary Pharmacology and Toxicology 8th Congress; Jerusalem, Israel, 30 July–3 August 2000.

24. Ziv, G.; Bogin, E.; Shani, J.; Sulman, F.G. Distribution and blood-to-milk transfer of labeled antibiotics. Antimicrob. Agents Chemother.; 1973; 3, pp. 607-613. [DOI: https://dx.doi.org/10.1128/AAC.3.5.607]

25. European Medicines Agency Committee for Veterinary Medicinal Products. Dihydrostreptomycin (Extrapolation to All Ruminants) Summary Report (4); EMEA/CVMP/211249/2005-Final European Medicines Agency Committee for Veterinary Medicinal Products: Amsterdam, The Netherlands, 2005; Volume 211249, pp. 1-5.

26. Friedlander, L.G.; Stephany, R.W. Dihydrostreptomycin and Streptomycin Addendum. Residues Some Vet. Drugs Anim. Foods; 2002; 41, pp. 37-41.

27. Lohuis, J.; Poutrel, B.; Cremoux, R.; Parez, V.; Aguer, D. Milk residues of penicillin, nafcillin and dihydrostreptomycin in dairy goats postpartum treated with Nafpenzal N8 at drying-off. Proceedings of the Residues of Antimicrobial Drugs and Other Inhibitors in Milk; Kiel, Germany, 28–31 August 1995.

28. Lohuis, J.; Berthelot, X.; Cester, C.; Parez, V.; Aguer, D. Pharmacokinetics and milk residues of penicillin, nafcillin and dihydrostreptomycin in dairy sheep treated with nafpenzal DC at drying-off. Proceedings of the Residues of Antimicrobial Drugs and Other Inhibitors in Milk; Kiel, Germany, 28–31 August 1995.

29. Ziv, G.; Bogin, E.; Shani, J.; Sulman, F. Penetration of radioactive-labeled antibiotics from blood serum into milk in normal and mastitic ewes. Ann. Rech. Vét.; 1974; 5, pp. 15-28.

30. European Medicines Agency Committee for Veterinary Medicinal Products. Streptomycin and Dihydrostreptomycin Summary Report (2); EMEA/MRL/728/00-Final European Medicines Agency Committee for Veterinary Medicinal Products: Amsterdam, The Netherlands, 2000; Volume 728, pp. 1-7.

31. Heitzman, R.J. Dihydrostreptomycin/Streptomycin Addendum. Residues Some Vet. Drugs Anim. Foods; 1998; 41, pp. 39-44.

32. Toutain, P.; De Pomyers, H.; Larrieu, G.; Periquet, B.; More, J. An in vivo model for pharmacokinetic studies in the kidney. J. Pharmacol. Methods; 1985; 14, pp. 1-11. [DOI: https://dx.doi.org/10.1016/0160-5402(85)90038-5]

33. Andreini, G.; Pignattelli, P. Kanamycin blood levels and residues in domestic animals. Vet. Milano; 1972; 21, pp. 51-72.

34. Pfizer, Inc. ANADA 200-046 Neomycin Sulfate Soluble Powder 325 g/lb—Supplemental Approval (3 April 1996); FOI—Neomycin ANADA 200-046 Pfizer: New York, NY, USA, 1996; pp. 1-3.

35. Lavy, E.; Ziv, G.; Glickman, A. Single-dose pharmacokinetics of thiamphenicol in lactating goats. Acta Vet. Scand. Suppl.; 1991; 87, pp. 99-102.

36. Lavy, E.; Ziv, G.; Soback, S.; Glickman, A.; Winkler, M. Clinical pharmacology of florfenicol in lactating goats. Acta Vet. Scand. Suppl.; 1991; 87, pp. 133-136.

37. Government of Canada. Questions and Answers on Health Canada’s Policy on Extra-Label Drug Use (ELDU) in Food-Producing Animals; Government of Canada: Ottowa, ON, Canada, 2009.

38. European Food Safety Authority. Scientific Opinion on Chloramphenicol in Food and Feed; European Food Safety Authority: Parma, Italy, 2014; [DOI: https://dx.doi.org/10.2903/j.efsa.2014.3907]

39. Ziv, G.; Bogin, E.; Sulman, F. Blood and milk levels of chloramphenicol in normal and mastitic cows and ewes after intramuscular administration of chloramphenicol and chloramphenicol sodium succinate. Zent. Vet. Reihe A; 1973; 20, pp. 801-811. [DOI: https://dx.doi.org/10.1111/j.1439-0442.1973.tb01057.x]

40. Dagorn, M.; Guillot, P.; Sanders, P. Pharmacokinetics of chloramphenicol in sheep after intravenous, intramuscular and subcutaneous administration. Vet. Q.; 1990; 12, pp. 166-174. [DOI: https://dx.doi.org/10.1080/01652176.1990.9694262]

41. Ziv, G. Pharmacokinetics of antimycoplasma antibiotics in dairy cows and ewes. Proceedings of the 8th International Meeting of Diseases in Cattle; Milan, Italy, 9–13 September 1974; pp. 80-92.

42. Wetzlich, S.E.; Lane, V.M.; Craigmill, A.L. Tissue residue depletion after multiple subcutaneous administration of florfenicol to sheep. Proceedings of the European Association of Veterinary Pharmacology and Toxicology 10th Congress; Turin, Italy, 17–22 September 2006; Volume 29, pp. 154-155.

43. Lane, V.M.; Villarroel, A.; Wetzlich, S.; Clifford, A.; Taylor, I.; Craigmill, A. Tissue residues of florfenicol in sheep. J. Vet. Pharmacol. Ther.; 2008; 31, pp. 178-180. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2007.00918.x]

44. Wells, R.J. Thiamphenicol; Addendum to the thiamphenicol residue monograph prepared by the 47th meeting of the Committee and published in FAO Food and Nutrition Paper 41/9, Rome 1996. Residues Some Vet. Drugs Anim. Foods; 2000; 41, pp. 119-128.

45. Roy, B.; Banerjee, N. Distribution of chloramphenicol in goat blood and milk after intramuscular administration. Indian J. Anim. Sci.; 1983; 53, pp. 847-849.

46. Wal, J.-M.; Peleran, J.-C.; Bories, G.F. High performance liquid chromatographic determination of chloramphenicol in milk. J. Assoc. Off. Anal. Chem.; 1980; 63, pp. 1044-1048. [DOI: https://dx.doi.org/10.1093/jaoac/63.5.1044]

47. Ziv, G.; Nouws, J. Serum and milk concentrations of ampicillin and amoxycillin in ruminants. Refuah Vet.; 1979; 36, pp. 104-110.

48. Ramos, F.; Boison, J.; Friedlander, L.G. Amoxicillin. Residues Some Vet. Drugs Anim. Foods; 2012; pp. 1-35. Available online: https://www.fao.org/fileadmin/user_upload/vetdrug/docs/12-2012-amoxicillin.pdf (accessed on 7 August 2022).

49. Buswell, J.; Knight, C.; Barber, D. Antibiotic persistence and tolerance in the lactating goat following intramammary therapy. Vet. Rec.; 1989; 125, pp. 301-303. [DOI: https://dx.doi.org/10.1136/vr.125.11.301]

50. Roncada, P.; Tomasi, L.; Stracciari, G.; Ermini, L.; Strocchia, A. Milk depletion of dicloxacillin residues in cows and sheep following intramammary administration. J. Vet. Pharmacol. Ther.; 2000; 23, pp. 237-241. [DOI: https://dx.doi.org/10.1046/j.1365-2885.2000.00257.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11126324]

51. Buswell, J.; Barber, D. Antibiotic persistence and tolerance in the lactating sheep following a course of intramammary therapy. Br. Vet. J.; 1989; 145, pp. 552-557. [DOI: https://dx.doi.org/10.1016/0007-1935(89)90117-6]

52. Pengov, A.; Kirbis, A. Risks of antibiotic residues in milk following intramammary and intramuscular treatments in dairy sheep. Anal. Chim. Acta; 2009; 637, pp. 13-17. [DOI: https://dx.doi.org/10.1016/j.aca.2008.09.021] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19286006]

53. Hill, B.; Jagusch, K.; Rajan, L.; Kidd, G. Antibiotic residues in goats milk following intramammary treatment. N. Z. Vet. J.; 1984; 32, pp. 130-131. [DOI: https://dx.doi.org/10.1080/00480169.1984.35094]

54. Ferrini, A.M.; Trenta, S.; Mannoni, V.; Rosati, R.; Coni, E. Depletion of long-acting ampicillin in goat milk following intramuscular administration. J. Agric. Food Chem.; 2010; 58, pp. 12199-12203. [DOI: https://dx.doi.org/10.1021/jf102351p]

55. Boatto, G.; Cerri, R.; Pau, A.; Palomba, M.; Pintore, G.; Denti, M.G. Monitoring of benzylpenicillin in ovine milk by HPLC. J. Pharm. Biomed. Anal.; 1998; 17, pp. 733-738. [DOI: https://dx.doi.org/10.1016/S0731-7085(97)00245-8]

56. Gee, H.-E.; Ho, K.-B.; Toothill, J. Liquid chromatographic determination of benzylpenicillin and cloxacillin in animal tissues and its application to a study of the stability at –20 °C of spiked and incurred residues of benzylpenicillin in ovine liver. J. AOAC Int.; 1996; 79, pp. 640-644. [DOI: https://dx.doi.org/10.1093/jaoac/79.3.640]

57. Longo, F.; Cozzani, R.; Santis, L.d.; Boselli, C.; Rosati, R.; Fagiolo, A.; Cinquina, A. Amoxicillin detection in milk using screening tests and liquid chromatography after administration to lactating sheep. Riv. Sci. Dell’alimentazione; 2002; 31, pp. 313-319.

58. Chaleva, E.; Dincheva, E. Ampicillin tolerance and content in the mammary gland of lactating cows and sheep. Vet. Med. Nauk.; 1977; 14, pp. 73-78.

59. Edwards, S. Penicillin levels in the milk following intramuscular injection. Vet. Rec.; 1966; 78, pp. 583-585. [DOI: https://dx.doi.org/10.1136/vr.78.17.583]

60. Long, P.; Heavner, J.; Ziv, G.; Geleta, J.; Nepote, K. Depletion of antibiotics from the mammary gland of goats. J. Dairy Sci.; 1984; 67, pp. 707-712. [DOI: https://dx.doi.org/10.3168/jds.S0022-0302(84)81357-0]

61. Norbrook Laboratories, Ltd. Freedom of Information Summary, Supplemental New Animal Drug Application, NADA 065-010. Norocillin (Penecillin G Procaine Injectable Suspension) Cattle, Sheep, Swine, and Horses; To Revise the Currently Approved Formulation to Include Lecithin as a Surfactant; FOI—Norocillin NADA 065-010 Norbrook Laboratories, Ltd.: Newry, UK, 2010; pp. 1-27.

62. Rule, R.; Lacchini, R.; Mordujovich, P.; Antonini, A. Evaluation of cefepime kinetic variables and milk production volume in goats. Arq. Bras. Med. Vet. Zootec.; 2004; 56, pp. 116-118. [DOI: https://dx.doi.org/10.1590/S0102-09352004000100018]

63. Badillo, E.; Escudero, E.; Hernandis, V.; Galecio, J.S.; Marín, P. Pharmacokinetics of cefonicid in lactating goats after intravenous, intramuscular and subcutaneous administration, and after a long-acting formulation for subcutaneous administration. J. Vet. Pharmacol. Ther.; 2020; 43, pp. 50-56. [DOI: https://dx.doi.org/10.1111/jvp.12825]

64. Yadav, K.; Jayachandran, C.; Singh, M.; Jha, H.; Sinha, S. Kinetics of intravenously administered ceftriaxone in lactating goat. Indian J. Anim. Sci.; 2013; 70, pp. 163-165.

65. Ismail, M. Pharmacokinetics, urinary and mammary excretion of ceftriaxone in lactating goats. J. Vet. Med. Ser. A; 2005; 52, pp. 354-358. [DOI: https://dx.doi.org/10.1111/j.1439-0442.2005.00744.x]

66. Ziv, G.; Nouws, J. Clinical pharmacology of cephacetrile in ruminants. Zent. Vet. Reihe B; 1977; 24, pp. 798-811. [DOI: https://dx.doi.org/10.1111/j.1439-0450.1977.tb00972.x]

67. El Badawy, S.; Amer, A.; Kamel, G.; Eldeib, K.; Constable, P. Comparative pharmacokinetics using a microbiological assay and high performance liquid chromatography following intravenous administration of cefquinome in lactating goats with and without experimentally induced Staphylococcus aureus mastitis. Small Rumin. Res.; 2015; 133, pp. 67-76. [DOI: https://dx.doi.org/10.1016/j.smallrumres.2015.11.004]

68. El Badawy, S.A.; Amer, A.M.; Kamel, G.M.; Eldeib, K.M.; Constable, P.D. Pharmacokinetics and pharmacodynamics of intramammary cefquinome in lactating goats with and without experimentally induced Staphylococcus aureus mastitis. J. Vet. Pharmacol. Ther.; 2019; 42, pp. 452-460. [DOI: https://dx.doi.org/10.1111/jvp.12790]

69. Soback, S.; Ziv, G.; Bor, A.; Shapira, M. Pharmacokinetics of cephalexin glycinate in lactating cows and ewes. Zent. Vet. Reihe A; 1988; 35, pp. 755-760.

70. Wetzel, R.K.; Stayer, P.A.; Wildman, E.E.; Randy, H.A. Depletion of cephapirin in goat’s milk following intramammary infusion. J. Dairy Sci.; 1986; 69, 245.

71. Courtin, F.; Wetzlich, S.; Gustafson, C.; Craigmill, A. Pharmacokinetics and milk residues of ceftiofur and metabolites in dairy goats. Proceedings of the European Association of Veterinary Pharmacology and Toxicology 6th Congress; Edinburgh, UK, 7–11 August 1994; pp. 81-82.

72. El-Rabbat, N.A.; Abdel-Wadood, H.M.; Sayed, M.; Mousa, H.S. High-performance liquid chromatographic determination and pharmacokinetic study of cefepime in goat plasma and milk after pre-column derivatization with Hg (I). J. Sep. Sci.; 2010; 33, pp. 2599-2609. [DOI: https://dx.doi.org/10.1002/jssc.201000294]

73. Rule, R.; Villagra, S.; Barrena, P.; Lacchini, R.; Reynaldni, F.J. Pharmacokinetics of ceftazidime administered to lactating and non-lactating goats. J. S. Afr. Vet. Assoc.; 2011; 82, pp. 219-223. [DOI: https://dx.doi.org/10.4102/jsava.v82i4.77]

74. European Medicines Agency Committee for Veterinary Medicinal Products. Ceftiofur (Extension to Ovine and Extrapolation to All Mammalian Species) Summary Report (4); European Medicines Agency Committee for Veterinary Medicinal Products: Amsterdam, The Netherlands, 2006; Volume 80785, pp. 1-3.

75. Garrett, E.; Dirikolu, L.; Grover, G. Milk and serum concentration of ceftiofur following intramammary infusion in goats. J. Vet. Pharmacol. Ther.; 2015; 38, pp. 569-574. [DOI: https://dx.doi.org/10.1111/jvp.12217]

76. Goudah, A.; Shin, H.; Shim, J.; El-Aty, A.A. Characterization of the relationship between serum and milk residue disposition of ceftriaxone in lactating ewes. J. Vet. Pharmacol. Ther.; 2006; 29, pp. 307-312. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2006.00749.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16846468]

77. Rageh, A.H.; Abdel-Rahim, S.A.; Askal, H.F.; Saleh, G.A. Hydrophilic-interaction planar chromatography in ultra-sensitive determination of α-aminocephalosporin antibiotics. Application to analysis of cefalexin in goat milk samples using modified QuEChERS extraction technique. J. Pharm. Biomed. Anal.; 2019; 166, pp. 421-434. [DOI: https://dx.doi.org/10.1016/j.jpba.2019.01.001] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30716654]

78. Rule, R.; Cordiviola, C.; Vita, M.; Lacchini, R. Correlations between milk production and kinetic variables in milk of cephalothin administered to lactating goats. Vet. Med.; 2004; 49, 370. [DOI: https://dx.doi.org/10.17221/5725-VETMED]

79. Rule, R.; Lacchini, R.; Román, A.G.; Antonini, A.; de Buschiazzo, P. Influence of feed type on the pharmacokinetics of cephalothin administered to lactating goats. Arch. Zootec.; 2007; 56, pp. 807-815.

80. El-Sayed, M.; Atef, M.; El-Komy, A. Disposition kinetics of cephradine in normal and Escherichia coli infected goats. Dtsch. Tierarztl. Wochenschr.; 1994; 101, pp. 56-60.

81. Singh, C.S.; Singh, S.D.; Singh, M.K.; Jayachandran, C. Disposition kinetics and distribution of ciprofloxacin in biological fluids of goats after intravenous administration. Indian J. Anim. Sci.; 2001; 71, pp. 635-637.

82. El-Banna, H.; El-Sooud, K.A. Disposition kinetics of ciprofloxacin in lactating goats. Dtsch. Tierarztl. Wochenschr.; 1998; 105, pp. 35-38.

83. Escudero, E.; Cárceles, C.; Fernandez-Varon, E.; Marin, P.; Benchaoui, H. Pharmacokinetics of danofloxacin 18% in lactating sheep and goats. J. Vet. Pharmacol. Ther.; 2007; 30, pp. 572-577. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2007.00898.x]

84. Escudero, E.; Marín, P.; Cárceles, C.M.; Ramírez, M.J.; Fernández-Varón, E. Pharmacokinetic and milk penetration of a difloxacin long-acting poloxamer gel formulation with carboxy-methylcellulose in lactating goats. Vet. J.; 2011; 188, pp. 92-95. [DOI: https://dx.doi.org/10.1016/j.tvjl.2010.03.008]

85. El-Sooud, K.A. Influence of albendazole on the disposition kinetics and milk antimicrobial equivalent activity of enrofloxacin in lactating goats. Pharmacol. Res.; 2003; 48, pp. 389-395. [DOI: https://dx.doi.org/10.1016/S1043-6618(03)00179-8]

86. Marin, P.; Escudero, E.; Fernandez-Varon, E.; Espuny, A.; Titos, J.; Hernandis, V.; Carceles, C. Pharmacokinetics and milk penetration of an enrofloxacin long-acting poloxamer 407 gel formulation in lactating goats. J. Vet. Pharamcol. Ther.; 2009; 32, pp. 195-196.

87. Narayan, J.P.; Kumar, N.; Jha, H.; Jayachandran, C. Effect of probenecid on kinetics of enrofloxacin in lactating goats after subcutaneous administration. Indian J. Exp. Biol.; 2009; 47, pp. 53-56.

88. Haritova, A.; Lashev, L.; Pashov, D. Pharmacokinetics of enrofloxacin in lactating sheep. Res. Vet. Sci.; 2003; 74, pp. 241-245. [DOI: https://dx.doi.org/10.1016/S0034-5288(03)00003-1]

89. Marín, P.; Cárceles, C.M.; Escudero, E.; Fernández-Varón, E. Pharmacokinetics and milk penetration of ibafloxacin after intravenous administration to lactating goats. Can. J. Vet. Res.; 2007; 71, 74.

90. Goudah, A.; Abo-El-Sooud, K. Pharmacokinetics, urinary excretion and milk penetration of levofloxacin in lactating goats. J. Vet. Pharmacol. Ther.; 2009; 32, pp. 101-104. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2008.01001.x]

91. Lorenzutti, A.; Litterio, N.; Himelfarb, M.; Zarazaga, M.D.P.; Andrés, M.S.; De Lucas, J. Pharmacokinetics, milk penetration and PK/PD analysis by Monte Carlo simulation of marbofloxacin, after intravenous and intramuscular administration to lactating goats. J. Vet. Pharmacol. Ther.; 2017; 40, pp. 629-640. [DOI: https://dx.doi.org/10.1111/jvp.12409]

92. Shem-Tov, M.; Ziv, G.; Glickman, A.; Saran, A. Pharmacokinetics and penetration of marbofloxacin from blood into the milk of cows and ewes. J. Vet. Med. Ser. A; 1997; 44, pp. 511-519. [DOI: https://dx.doi.org/10.1111/j.1439-0442.1997.tb01137.x]

93. Fernández-Varón, E.; Villamayor, L.; Escudero, E.; Espuny, A.; Cárceles, C.M. Pharmacokinetics and milk penetration of moxifloxacin after intravenous and subcutaneous administration to lactating goats. Vet. J.; 2006; 172, pp. 302-307. [DOI: https://dx.doi.org/10.1016/j.tvjl.2005.04.017]

94. Goudah, A.; Cho, H.J.; Shin, H.C.; Shim, J.H.; Regmi, N.L.; Shimoda, M.; Abd El-Aty, A.M. Pharmacokinetics and milk distribution characteristics of orbifloxacin following intravenous and intramuscular injection in lactating ewes. J. Vet. Pharmacol. Ther.; 2009; 32, pp. 338-344. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2008.01046.x]

95. El-Aty, A.M.A.; Goudah, A. Some pharmacokinetic parameters of pefloxacin in lactating goats. Vet. Res. Commun.; 2002; 26, pp. 553-561. [DOI: https://dx.doi.org/10.1023/A:1020243615928]

96. Real, R.; Egido, E.; Pérez, M.; Gonzalez-Lobato, L.; Barrera, B.; Prieto, J.; Alvarez, A.; Merino, G. Involvement of breast cancer resistance protein (BCRP/ABCG2) in the secretion of danofloxacin into milk: Interaction with ivermectin. J. Vet. Pharmacol. Ther.; 2011; 34, pp. 313-321. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2010.01241.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20950350]

97. Perez, M.; Otero, J.A.; Barrera, B.; Prieto, J.G.; Merino, G.; Alvarez, A.I. Inhibition of ABCG2/BCRP transporter by soy isoflavones genistein and daidzein: Effect on plasma and milk levels of danofloxacin in sheep. Vet. J.; 2013; 196, pp. 203-208. [DOI: https://dx.doi.org/10.1016/j.tvjl.2012.09.012] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23083838]

98. Pulido, M.M.; Molina, A.J.; Merino, G.; Mendoza, G.; Prieto, J.G.; Alvarez, A.I. Interaction of enrofloxacin with breast cancer resistance protein (BCRP/ABCG2): Influence of flavonoids and role in milk secretion in sheep. J. Vet. Pharmacol. Ther.; 2006; 29, pp. 279-287. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2006.00744.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16846465]

99. Shem-Tov, M.; Ziv, G.; Glickman, A.; Saran, A. Pharmacokinetics and penetration of danofloxacin from the blood into the milk of ewes. Vet. Res.; 1997; 28, pp. 571-579.

100. Barrera, B.; González-Lobato, L.; Otero, J.A.; Real, R.; Prieto, J.G.; Álvarez, A.I.; Merino, G. Effects of triclabendazole on secretion of danofloxacin and moxidectin into the milk of sheep: Role of triclabendazole metabolites as inhibitors of the ruminant ABCG2 transporter. Vet. J.; 2013; 198, pp. 429-436. [DOI: https://dx.doi.org/10.1016/j.tvjl.2013.07.033]

101. Otero, J.A.; García-Mateos, D.; Alvarez-Fernández, I.; García-Villalba, R.; Espín, J.C.; Álvarez, A.I.; Merino, G. Flaxseed-enriched diets change milk concentration of the antimicrobial danofloxacin in sheep. BMC Vet. Res.; 2018; 14, 14. [DOI: https://dx.doi.org/10.1186/s12917-018-1341-3]

102. Marín, P.; Escudero, E.; Fernández-Varón, E.; Ramírez, M.; Cárceles, C. Pharmacokinetics and milk penetration of difloxacin after a long-acting formulation for subcutaneous administration to lactating goats. J. Dairy Sci.; 2010; 93, pp. 3056-3064. [DOI: https://dx.doi.org/10.3168/jds.2010-3257]

103. Fernandez-Varon, E.; Escudero, E.; Marin, P.; Titos, J.; Espuny, A.; Carceles, C. Pharmacokinetics and milk penetration of enrofloxacin and its metabolite ciprofloxacin after subcutaneous administration to lactating goats. J. Vet. Pharmacol. Ther.; 2009; 32, pp. 196-197.

104. European Medicines Agency Committee for Veterinary Medicinal Products. Enrofloxacin (Extension to Sheep, Rabbits and Lactating Cows) Summary Report (3); EMEA/MRL/389/98-Final European Medicines Agency Committee for Veterinary Medicinal Products: Amsterdam, The Netherlands, 1998; Volume 389, pp. 1-5.

105. Cárceles, C.M.; Villamayor, L.; Escudero, E.; Marín, P.; Fernández-Varón, E. Pharmacokinetics and milk penetration of moxifloxacin after intramuscular administration to lactating goats. Vet. J.; 2007; 173, pp. 452-455. [DOI: https://dx.doi.org/10.1016/j.tvjl.2005.11.003]

106. Soback, S.; Gips, M.; Bialer, M.; Bor, A. Effect of lactation on single-dose pharmacokinetics of norfloxacin nicotinate in ewes. Antimicrob. Agents Chemother.; 1994; 38, pp. 2336-2339. [DOI: https://dx.doi.org/10.1128/AAC.38.10.2336]

107. Marín, P.; Escudero, E.; Fernández-Varón, E.; Cárceles, C. Pharmacokinetics and milk penetration of orbifloxacin after intravenous, subcutaneous, and intramuscular administration to lactating goats. J. Dairy Sci.; 2007; 90, pp. 4219-4225. [DOI: https://dx.doi.org/10.3168/jds.2007-0071]

108. Delmas, J.; Chapel, A.; Gaudin, V.; Sanders, P. Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration: Bioavailability and tissue residue studies. J. Vet. Pharmacol. Ther.; 1997; 20, pp. 249-257. [DOI: https://dx.doi.org/10.1046/j.1365-2885.1997.00067.x]

109. Francis, P.G.; Wells, R.J. Flumequine. Residues Some Vet. Drugs Anim. Foods; 1998; 41, pp. 59-70.

110. European Medicines Agency Committee for Veterinary Medicinal Products. Erythromycin Summary Report (2); EMEA/MRL/720/99-Final European Medicines Agency Committee for Veterinary Medicinal Products: Amsterdam, The Netherlands, 2000; Volume 720, pp. 1-8.

111. Goudah, A.; Sher Shah, S.; Shin, H.; Shim, J.; Abd El-Aty, A. Pharmacokinetics and mammary residual depletion of erythromycin in healthy lactating ewes. J. Vet. Med. Ser. A; 2007; 54, pp. 607-611. [DOI: https://dx.doi.org/10.1111/j.1439-0442.2007.00986.x]

112. Ramadan, A. Pharmacokinetics of tilmicosin in serum and milk of goats. Res. Vet. Sci.; 1997; 62, pp. 48-50. [DOI: https://dx.doi.org/10.1016/S0034-5288(97)90179-X]

113. MacNeil, J.D. Tilmicosin. Residues Some Vet. Drugs Anim. Foods; 1997; 41, pp. 106-118.

114. Xu, S.; Arnold, D. Tilmicosin: Addendum to tho monographs prepared by the 47th meeting of the Committee and published in the FAO Food and Nutrition paper 41/9. Residues Some Vet. Drugs Anim. Foods; 2008; 41, pp. 1-37.

115. Grismer, B.; Rowe, J.D.; Carlson, J.; Wetzlich, S.; Tell, L.A. Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (C apra hircus). J. Vet. Pharmacol. Ther.; 2014; 37, pp. 205-208. [DOI: https://dx.doi.org/10.1111/jvp.12071]

116. Amer, A.; Constable, P.; Goudah, A.; El Badawy, S. Pharmacokinetics of tulathromycin in lactating goats. Small Rumin. Res.; 2012; 108, pp. 137-143. [DOI: https://dx.doi.org/10.1016/j.smallrumres.2012.07.003]

117. Lin, Z.; Cuneo, M.; Rowe, J.D.; Li, M.; Tell, L.A.; Allison, S.; Carlson, J.; Riviere, J.E.; Gehring, R. Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach. BMC Vet. Res.; 2016; 12, 258. [DOI: https://dx.doi.org/10.1186/s12917-016-0884-4]

118. Atef, M.; Youssef, S.; Atta, A.; El-Maaz, A. Disposition of tylosin in goats. Dtsch. Tierarztl. Wochenschr.; 1991; 98, pp. 451-453. [DOI: https://dx.doi.org/10.1016/0007-1935(91)90045-O]

119. Ziv, G.; Sulman, F.G. Serum and milk concentrations of spectinomycin and tylosin in cows and ewes. Am. J. Vet. Res.; 1973; 34, pp. 329-333.

120. Nagy, J.; Popelka, P.; Sokol, J.; Turek, P.; Neuschl, J. The excretion of tylosin residues in ewes milk after its experimental administration. Folia Vet.; 2001; 45, pp. 196-198.

121. Ambros, L.; Montoya, L.; Kreil, V.; Waxman, S.; Albarellos, G.; Rebuelto, M.; Hallu, R.; Andres, M.S. Pharmacokinetics of erythromycin in nonlactating and lactating goats after intravenous and intramuscular administration. J. Vet. Pharmacol. Ther.; 2007; 30, pp. 80-85. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2007.00819.x]

122. Ziv, G. Concentrations and residues of antibiotics in the milk of goats after parenteral and intramammary administration. Proceedings of the Symposium Internacional de Ordeno Mecanico de Pequenos Rumiantes; Valladolid, Spain, 1984; pp. 513-528.

123. Romanet, J.; Smith, G.W.; Leavens, T.L.; Baynes, R.E.; Wetzlich, S.E.; Riviere, J.E.; Tell, L.A. Pharmacokinetics and tissue elimination of tulathromycin following subcutaneous administration in meat goats. Am. J. Vet. Res.; 2012; 73, pp. 1634-1640. [DOI: https://dx.doi.org/10.2460/ajvr.73.10.1634]

124. Clothier, K.A.; Leavens, T.; Griffith, R.W.; Wetzlich, S.E.; Baynes, R.E.; Riviere, J.E.; Tell, L.A. Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus). J. Vet. Pharmacol. Ther.; 2012; 35, pp. 113-120. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2011.01300.x]

125. Kellermann, M.; Huang, R.A.; Forbes, A.B.; Rehbein, S. Gamithromycin plasma and skin pharmacokinetics in sheep. Res. Vet. Sci.; 2014; 97, pp. 199-203. [DOI: https://dx.doi.org/10.1016/j.rvsc.2014.08.008]

126. European Medicines Agency Committee for Veterinary Medicinal Products. European Public MRL Assessment Report (EPMAR) Gamithromycin (All Ruminants Except Bovine Species.)12 December 2016; EMA/CVMP/454092/2016 European Medicines Agency Committee for Veterinary Medicinal Products EPMAR: Amsterdam, The Netherlands, 2016; Volume 454092, pp. 1-11.

127. Atef, M.; El-Sooud, K.A.; Nahed, E.; Tawfik, M. Elimination of tilmicosin in lactating ewes. Dtsch. Tierarztl. Wochenschr.; 1999; 106, pp. 291-294.

128. Parker, R.; Patel, R.; Mclaren, I.; Francis, P. Residues of tilmicosin in milk of sheep after subcutaneous administration. Proceedings of the European Association for Veterinary Pharmacology and Toxicology; Edinburgh, UK, 7–11 August 1994; pp. 226-227.

129. Elanco Animal Health. Freedom of Information Summary; Micotil 300 Injection (tilmicosin phosphate); Supplement to NADA 140-929 Date of Approval: 4 September 2002 FOI—Micotil NADA 140-929 Elanco Animal Health: Greenfield, IN, USA, 2002; pp. 1-14.

130. European Medicines Agency Committee for Veterinary Medicinal Products. European Public MRL Assessment Report (EPMAR) Tulathromycin (Ovine and Caprine Species) 23 February 2015; EMA/CVMP/131462/2014 European Medicines Agency Committee for Veterinary Medicinal Products EPMAR: Amsterdam, The Netherlands, 2015; Volume 131462, pp. 1-11.

131. Tunnicliff, E.; Swingle, K. Sulfonamide concentrations in milk and plasma from normal and mastitic ewes treated with sulfamethazine. Am. J. Vet. Res.; 1965; 26, pp. 920-927.

132. Rasmussen, F. Mammary excretion of sulphonamides. Acta Pharmacol. Toxicol.; 1958; 15, pp. 139-148. [DOI: https://dx.doi.org/10.1111/j.1600-0773.1958.tb00292.x]

133. Akogwu, E.; Saganuwan, S.; Onyeyili, P. Effects of piroxicam on tissue distribution of sulfadimidine in west African dwarf male and female goats. Hum. Exp. Toxicol.; 2018; 37, pp. 61-68. [DOI: https://dx.doi.org/10.1177/0960327117692135] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28176534]

134. Bevill, R.; Sharma, R.; Meachum, S.; Wozniak, S.; Bourne, D.; Dittert, L. Disposition of sulfonamides in food-producing animals: Concentrations of sulfamethazine and its metabolites in plasma, urine, and tissues of lambs following intravenous administration. Am. J. Vet. Res.; 1977; 38, pp. 973-977. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/883725]

135. Jha, H.; Banerjee, N. A note on distribution of sulphadimethoxine in blood, milk and urine of goats. Indian J. Anim. Sci.; 1977; 47, pp. 496-497.

136. Yndestad, M.; Underdal, B. Residues of Sulfadimidine/Sulfanilamide and Sulfamethoxypyridazine in Sheep Tissue. Acta Vet. Scand.; 1977; 18, pp. 15-22. [DOI: https://dx.doi.org/10.1186/BF03548461] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/848402]

137. Bevill, R.F.; Koritz, G.D.; Dittert, L.W.; Bobrne, D.W. Disposition of sulfonamides in food-producing animals V: Disposition of sulfathiazole in tissue, urine, and plasma of sheep following intravenous administration. J. Pharm. Sci.; 1977; 66, pp. 1297-1300. [DOI: https://dx.doi.org/10.1002/jps.2600660923]

138. Righter, H.F.; Worthington, J.M.; Mercer, H.D. Tissue residue depletion of sulfamerazine in sheep. J. Agric. Food Chem.; 1972; 20, pp. 876-878. [DOI: https://dx.doi.org/10.1021/jf60182a034]

139. Atef, M. Half-life, volume of distribution and acetylation of sulphamerazine in sheep. Zent. Vet. Reihe A; 1978; 25, pp. 585-591. [DOI: https://dx.doi.org/10.1111/j.1439-0442.1978.tb00960.x]

140. Bulgin, M.; Lane, V.M.; Archer, T.; Baggot, J.; Craigmill, A. Pharmacokinetics, safety and tissue residues of sustained-release sulfamethazine in sheep. J. Vet. Pharmacol. Ther.; 1991; 14, pp. 36-45. [DOI: https://dx.doi.org/10.1111/j.1365-2885.1991.tb00802.x]

141. Bevill, R.F. Application of Pharamcokinetics to the Study of Sulfonamide Behavior in Cattle, Sheep, and Swine. Proceedings of the Symposium of Veterinary Pharmacology and Therapeutics; Baton Rouge, LA, USA, 13–15 March 1978; pp. 75-101.

142. Paulson, G.; Struble, C.; Mitchell, A. Comparative metabolism of sulfamethazine [4-amino-N-(4,6-dimethyl-2-pyrimidinyl) benzenesulfonamide] in the rat, chicken, pig and sheep. Mode of Action, Metabolism and Toxicology; Elsevier: Amsterdam, The Netherlands, 1983; pp. 375-380.

143. Hashem, M.; Tayeb, F.; El-Mekkawi, T. The level of some sulphonamide preparations in tissues and blood of cocks and sheep. J. Egypt. Vet. Med. Assoc.; 1980; 40, pp. 5-11.

144. Attaie, R.; Bsharat, M.; Mora-Gutierrez, A.; Woldesenbet, S. Short communication: Determination of withdrawal time for oxytetracycline in different types of goats for milk consumption. J. Dairy Sci.; 2015; 98, pp. 4370-4376. [DOI: https://dx.doi.org/10.3168/jds.2014-8616]

145. Payne, M.; Babish, J.; Bulgin, M.; Lane, M.; Wetzlich, S.; Craigmill, A. Serum pharmacokinetics and tissue and milk residues of oxytetracycline in goats following a single intramuscular injection of a long-acting preparation and milk residues following a single subcutaneous injection. J. Vet. Pharmacol. Ther.; 2002; 25, pp. 25-32. [DOI: https://dx.doi.org/10.1046/j.1365-2885.2002.00378.x]

146. Fletouris, D.; Papapanagiotou, E. Tissue residue depletion of oxytetracycline after repeated intramuscular administration of Oxysentin 100 in sheep. J. Vet. Pharmacol. Ther.; 2009; 32, pp. 56-61. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2008.01003.x]

147. Anifantakis, E.M. Excretion rates of antibiotics in milk of sheep and their effect on yogurt production. J. Dairy Sci.; 1982; 65, pp. 426-429. [DOI: https://dx.doi.org/10.3168/jds.S0022-0302(82)82208-X]

148. Wells, R.J. Chlortetracycline. Residues Some Vet. Drugs Anim. Foods; 1996; 41, pp. 31-66.

149. Jha, V.; Jayachandran, C.; Singh, M.; Singh, S. Pharmacokinetic data on doxycycline and its distribution in different biological fluids in female goats. Vet. Res. Commun.; 1989; 13, pp. 11-16. [DOI: https://dx.doi.org/10.1007/BF00366847]

150. Jayachandran, C.; Singh, M.; Singh, S.; Jha, H. Pharmacokinetics and distribution of minocydine in different biological fluids of goats after intravenous administration. Indian J. Anim. Sci.; 2012; 69, pp. 304-306.

151. Immelman, A.; Ziv, G. Serum and milk concentrations of oxytetracycline after the administration of a long-acting formulation to sheep. J. S. Afr. Vet. Assoc.; 1982; 53, pp. 199-200.

152. Arndt, T.; Robinson, D.; Holland, R.; Wetzlich, S.; Craigmill, A. Oxytetracycline residues in sheep following im dosing with a long-acting formulation. J. Vet. Pharmacol. Ther.; 1997; 20, pp. 314-315.

153. Boatto, G.; Pau, A.; Palomba, M.; Arenare, L.; Cerri, R. Monitoring of oxytetracycline in ovine milk by high-performance liquid chromatography. J. Pharm. Biomed. Anal.; 1999; 20, pp. 321-326. [DOI: https://dx.doi.org/10.1016/S0731-7085(99)00050-3]

154. Craigmill, A.; Holland, R.; Robinson, D.; Wetzlich, S.; Arndt, T. Serum pharmacokinetics of oxytetracycline in sheep and calves and tissue residues in sheep following a single intramuscular injection of a long-acting preparation. J. Vet. Pharmacol. Ther.; 2000; 23, pp. 345-352. [DOI: https://dx.doi.org/10.1046/j.1365-2885.2000.00292.x]

155. Fletouris, D.J.; Papapanagiotou, E.P. A new liquid chromatographic method for routine determination of oxytetracycline marker residue in the edible tissues of farm animals. Anal. Bioanal. Chem.; 2008; 391, pp. 1189-1198. [DOI: https://dx.doi.org/10.1007/s00216-007-1823-9] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18197400]

156. Fletouris, D.J.; Papapanagiotou, E.P.; Nakos, D.S. Liquid chromatographic determination and depletion profile of oxytetracycline in milk after repeated intramuscular administration in sheep. J. Chromatogr. B; 2008; 876, pp. 148-152. [DOI: https://dx.doi.org/10.1016/j.jchromb.2008.10.026] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18993118]

157. Cinquina, A.L.; Longo, F.; Barchi, D.; Fagiolo, A.; Rosati, R.; Cozzani, R. Comparative pharmacokinetics of oxytetracycline in goat and sheep milk. Residues of Veterinary Drugs in Food. Proceedings of the European Residue Conference IV; Veldhoven, The Netherlands, 8–10 May 2000; pp. 285-290.

158. Hassan, S.A.A.; Shaddad, S.A.I.; El-Tayeb, L.B.; Omer, M.A.; Al-Nazawi, M.H.; Homeida, A.M. Detection of long-acting oxytetracycline residue levels in tissue of desert sheep following intramuscular injection. Int. J. Pharmacol.; 2007; 3, pp. 299-301.

159. Reja, A.; Gonzalez, R.; Serrano, J.M.; Santiago, D.; Guimera, M.E.; Cano, M. Oxytetracycline and tetracycline residues in goat milk. Proceedings of the European Associations of Veterinary Pharmacology and Toxicology 6th Congress; Edinburgh, UK, 7–11 August 1994.

160. Reja Sanchez, A.; Gonzalez Pedrajas, R.; Serrano Caballero, J.M.; Santiago Laguna, D. Experimental determination of occurrence of tetracycline and oxytetracycline residues in goat milk. Blood/milk transference rates. Rev. Toxicol.; 1995; 12, pp. 29-34.

161. Cinquina, A.L.; Gianetti, L.; Barchi, D.; Lanzi, S.; Longo, F.; Coresi, A.; Fagiolo, A.; Cozzani, R. Oxytetracycline residues in goat milk. Obiettivi Doc. Vet.; 2002; 23, pp. 37-40.

162. Rule, R.; Moreno, L.; Serrano, J.M.; Garcia Roman, A.; Moyano, R.; Garcia, J. Pharmacokinetics and residues in milk of oxytetracyclines administered parenterally to dairy goats. Aust. Vet. J.; 2001; 79, pp. 492-496. [DOI: https://dx.doi.org/10.1111/j.1751-0813.2001.tb13023.x]

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