抗血小板薬をめぐる最近の話題　　２．遺伝子多型によるＣｌｏｐｉｄｏｇｒｅｌの効果への影響

概要

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In this study, we investigated whether the polymorphism of CYP2C19 affects the formation of active metabolite (AM) of clopidogrel and the antiplatelet effects of the AM in healthy subjects. In this single-dose study, 47 subjects were given 300 mg clopidogrel orally. 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), and also between EMs and the poor metabolizers (PMs, n=9). Moreover, the pharmacokinetic parameters of the AM correlated well with the inhibition of ADP-induced platelet aggregation (IPA) and the change in vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Individual differences in antiplatelet effects of clopidogrel were detected adequately by measuring IPA using aggregometer and VerifyNow and by analyzing the change in VASP phosphorylation. The CYP2C19 pharmacogenomic status is a determinant for AM formation and antiplatelet effects of clopidogrel in healthy subjects.
一般社団法人日本臨床薬理学会の論文