The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: A possible mechanism for clopidogrel resistance

K. A. Kim, P. W. Park, S. J. Hong, J. Y. Park

Research output: Contribution to journalArticle

252 Citations (Scopus)

Abstract

We evaluated the effect of the CYP2C19 genotype on the pharmacokinetics and pharmacodynamcis of clopidogrel. Twenty-four subjects were divided into three groups on the basis of their CYP2C19 genotype: homozygous extensive metabolizers (homoEMs, n = 8), heterozygous EMs (heteroEMs, n = 8), and poor metabolizers (PMs, n = 8). After a single 300-mg loading dose of clopidogrel on day 1, followed by a 75-mg daily maintenance dose from days 2 to 7, we measured the plasma levels of clopidogrel and assessed the antiplatelet effect as pharmacodynamics. The mean clopidogrel area under the curve (AUC) for PMs was 1.8- and 2.9-fold higher than that for heteroEMs and homoEMs, respectively (P = 0.013). The mean peak plasma concentration in PMs was 1.8- and 4.7-fold higher than that of heteroEMs and homoEMs, respectively (P = 0.008). PMs exhibited a significantly lower antiplatelet effect than heteroEMs or homoEMs (P < 0.001). From these findings it is clear that the CYP2C19 genotype affects the plasma levels of clopidogrel and modulates the antiplatelet effect of clopidogrel.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume84
Issue number2
DOIs
Publication statusPublished - 2008 Aug

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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