Clopidogrel pharmacogenomics and risk of inadequate platelet inhibition: US FDA recommendations.
Antiplatelet therapy with clopidogrel is the current standard of care for coronary artery disease patients undergoing a percutaneous coronary intervention. However, approximately 25% of patients experience a subtherapeutic antiplatelet response. Clopidogrel is a prodrug that undergoes hepatic biotransformation by CYP2C19 into its active metabolite. Several studies have reported that, compared with wild-type individuals, CYP2C19 variant allele carriers exhibit a significantly lower capacity to metabolize clopidogrel into its active metabolite and inhibit platelet activation, and are therefore at significantly higher risk of adverse cardiovascular events. Consequently, the US FDA has recently changed clopidogrel's prescribing information to highlight the impact of CYP2C19 genotype on clopidogrel pharmacokinetics, pharmacodynamics and clinical response. Future studies remain necessary to develop effective personalized therapeutic strategies for CYP2C19 variant allele carriers and other individuals at risk for clopidogrel nonresponsiveness.
Ellis
Kyle J
KJ
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, CB# 7569, Kerr Hall, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-27569, USA.
Stouffer
George A
GA
McLeod
Howard L
HL
Lee
Craig R
CR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D006801:Humans; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000235:genetics; D058925:Receptors, Purinergic P2Y12; D012306:Risk; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine