Clinical pharmacogenomics of warfarin and clopidogrel.
Genetic polymorphisms significantly influence responses to warfarin and clopidogrel. Polymorphisms in the cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase genes change warfarin pharmacokinetics and pharmacodynamics, respectively. Because these polymorphisms influence warfarin dose requirements, they may primarily help determine therapeutic warfarin doses in patients who newly start on the drug. To assist in estimating therapeutic warfarin doses, the warfarin label provides a pharmacogenomic dosing table and various warfarin pharmacogenomic dosing algorithms are available. On the other hand, polymorphisms in the CYP2C19 gene affect clopidogrel pharmacokinetics. These polymorphisms may be useful to identify clopidogrel nonresponders who may benefit from taking an alternative antiplatelet agent such as prasugrel and ticagrelor. Although both drugs have pharmacogenomic tests available for clinical use, their clinical utilities have not been established and are currently being actively studied. In this review, clinical application of warfarin and clopidogrel pharmacogenomics will be focused. With the current level of evidence, potential patients who may get benefit from warfarin and clopidogrel pharmacogenomic testing will be discussed. In addition, the interpretation of the warfarin and clopidogrel test results and the current barriers to widespread use of warfarin and clopidogrel pharmacogenomic testing will be discussed.
Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA 94143, USA. shinj@pharmacy.ucsf.edu
Jaekyu
J
Shin
D000925:Anticoagulants / Q000493:pharmacokinetics / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D000077144:Clopidogrel; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D011110:Polymorphism, Genetic / Q000187:drug effects; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000493:pharmacokinetics / Q000494:pharmacology*
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D000077144:Clopidogrel; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D064417:Vitamin K Epoxide Reductases; D013988:Ticlopidine