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The Effect of CYP2C19 Polymorphism on the Pharmacokinetics and Pharmacodynamics of Clopidogrel: A Possible Mechanism for Clopidogrel Resistance

2008; Wiley; Volume: 84; Issue: 2 Linguagem: Inglês

10.1038/clpt.2008.20

1532-6535

Kyoung‐Ah Kim, PW Park, SJ Hong, Ji Young Park,

Pharmacology and Obesity Treatment

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. Clinical Pharmacology & Therapeutics (2008); 84, 2, 236–242 doi:10.1038/clpt.2008.20