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Patients vary widely in their response to drugs. Having an understanding of the pharmacokinetic and pharmacodynamic properties of various medications is important when assessing ethnic differences in drug response. Genetic factors can account for 20 to 95 percent of patient variability. Genetic polymorphisms for many drug-metabolizing enzymes and drug targets (e.g., receptors) have been identified. Although currently limited to a few pathways, pharmacogenetic testing may enable physicians to understand why patients react differently to various drugs and to make better decisions about therapy. Ultimately, this understanding may shift the medical paradigm to highly individualized therapeutic regimens. (Am Fam Physician. 2008;77(11):1553-1560. Copyright © 2008 American Academy of Family Physicians.)
Although patient response to drugs varies widely and the reasons for this are diverse and complex, experts estimate that genetic factors account for 20 to 95 percent of patient variability in response to individual drugs.1 Genetic influences on drug metabolism interact with other intrinsic (i.e., physiologic) and extrinsic (i.e., cultural, behavioral, and environmental) characteristics of a person to determine the outcome from treatment with any pharmacologic agent (Table 1).2
Although still in its infancy, the field of pharmacogenetics and pharmacogenomics already provides useful clinical information to enhance patient care and offers a growing potential to individualize drug therapy and improve clinical outcomes. This article reviews the leading areas in which genetic variations currently affect treatment and indicates a need for physicians to monitor this topic as genomic-based treatment guidelines become available.
Definitions
The study of genetic variations in drug response is called pharmacogenetics when studying an individual gene, or pharmacogenomics when studying all genes. a person's genotype is his or her genetic makeup. The term can pertain to all genes or to a specific gene. The phenotype is a person's outward physical appearance or function resulting from the interaction between the genotype and the environment. Genetic polymorphisms are naturally occurring variants in gene structure that occur in more than 1 percent of the population. Polymorphisms may influence a drug's action by changing its pharmacokinetics or its pharmacodynamics.
Pharmacokinetics
Pharmacokinetics is the study of the rate and extent of drug absorption, distribution, metabolism, and excretion. These processes determine the fate of a drug in the body. a combination of metabolism and excretion constitutes drug elimination from...