抄録
In a meta-analysis, 21% of patients treated with clopidogrel, an antagonist for P2Y12 receptors, achieved low or no ex vivo inhibition of ADP-induced platelet aggregation, which may be caused by CYP2C19 polymorphism. However, it remains unresolved whether or not the polymorphism of CYP2C19 would affect the pharmacokinetics of the active metabolite of clopidogrel (AM) and the pharmacodynamics of antiplatelet effects to the AM. Therefore, in this study, we investigated whether the polymorphism of CYP2C19 would affect the formation of the AM and the antiplatelet effects to the AM in healthy subjects. In single dose study, 300mg clopidogrel was orally given to 47 subjects. The mean AUC and Cmax of the AM differed significantly (P<0.05) between the extensive metabolizers (EMs, n=18) and the intermediate metabolizers (IMs, n=20), as well as between EMs and the poor metabolizers (PMs, n=9). Moreover, the pharmacokinetic parameters of the AM correlated well with ADP-induced platelet aggregation and the vasodilator-stimulated phosphoprotein phosphorylation ratio. In another study, 75mg clopidogrel was orally given to 10 different subjects for 7 days. The non- or lower responsiveness to clopidogrel in the PMs could not be improved by repeated administration. The CYP2C19 pharmacogenomic status is a determinant for the formation of the AM and antiplatelet effects in healthy subjects.
