Tailoring Drug Therapy Based on Genotype
Cavallari, Larisa H.
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Polymorphisms in genes encoding drug metabolizing enzymes, drug transporters, and drug targets can influence drug effects and contribute to inter-individual differences in drug response. Genotype for drug metabolizing enzymes and drug transporters can influence drug disposition in the body (pharmacokinetics), whereas genotype for drug targets may influence sensitivity to a drug (pharmacodynamics). In some cases, response to a particular drug is contingent on genotype for both drug disposition and drug target proteins. For example, warfarin dose requirements are influenced by both cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) genotypes. The goal of pharmacogenetics is to maximize drug effectiveness while limiting drug toxicity, based on an individual's DNA. Over 80 drugs now contain genetic information in their FDA-approved labeling. In addition to influencing warfarin dose requirements, genotype contributes to the efficacy of clopidogrel in coronary artery disease, risk for hypersensitivity reactions to abacavir in the treatment of human immunodeficiency virus, risk for statin-induced myopathy, and responses to numerous other drugs. Genetic information is routinely integrated into decisions regarding cancer chemotherapy and treatment for human immunodeficiency virus. Clinical implementation of pharmacogenetics is becoming a reality in other therapeutic areas, such as for patients requiring dual antiplatelet therapy following coronary artery stent implantation. In the future, it is possible that individuals will be broadly genotyped so that genetic information can guide drug therapy decisions throughout their lifetime.