Abstract

Context

Fuzheng Huayu recipe (FZHY) combined with entecavir (ETV) is used to treat the cirrhosis caused by chronic hepatitis B (CHB) infection.

Objective

To investigate the effect of FZHY on ETV pharmacokinetics under different conditions.

Materials and methods

A model of liver fibrosis was created by intraperitoneal injection of dimethylnitrosamine (DMN; 10 μg/kg) for 4 weeks in Wistar rats. Ultra-high-performance liquid chromatography–tandem mass spectrometry was used to determine the blood concentration of ETV. Pharmacokinetic characteristics of ETV (0.9 mg/kg) were investigated after co-administration with FZHY (0.55 g/kg) at certain time intervals in normal and model rats.

Results

The analytical method for ETV was validated at 0.5–50 μg/L with a correlation coefficient = 0.9996, lower limit of quantitation of 0.5 μg/L and mean accuracy of 104.18 ± 9.46%. Compared with the ETV-N group, the pharmacokinetic parameters of the EF-2 group did not change significantly, but that of the EF-0 group decreased in Cmax to 27.38 μg/L, in AUC0–t from 323.84 to 236.67 μg/h/L, and a delay in Tmax from 0.75 to 6.00 h; that of the EF-0 group presented a decrease in Cmax of 61.92%, delay in t1/2 of 2.45 h and delay in Tmax of 2.92 h. The t1/2e and Vd/F of ETV were increased significantly to 8.01 h and 24.38 L/kg in the ETV-M group.

Conclusions

The effects of FZHY on ETV pharmacokinetics were diminished with an increase of interval time. The best time to administer both drugs is >2 h apart.

Details

Title
Effects of Fuzheng Huayu recipe on entecavir pharmacokinetics in normal and dimethylnitrosamine-induced hepatic fibrosis rats
Author
Yang, Tao 1 ; Tian-Hui, Zheng 2 ; Zhao, Qiang 2 ; Liu, Wei 3 ; Shu-Ping, Li 3 ; Yan-Yan, Tao 4 ; Chang-Hong, Wang 3 ; Cheng-Hai, Liu 5 

 Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Cardiology, Institute of Cardiovascular Disease of Integrated Traditional Chinese Medicine and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China 
 Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China 
 Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai, China 
 Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Cardiology, Institute of Cardiovascular Disease of Integrated Traditional Chinese Medicine and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China 
 Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China 
Pages
1-7
Publication year
2020
Publication date
Dec 2020
Publisher
Taylor & Francis Ltd.
ISSN
13880209
e-ISSN
17445116
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2509429954
Copyright
© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.