The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: A possible mechanism for clopidogrel resistance
The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: A possible mechanism for clopidogrel resistance
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DOI：
10.1038/clpt.2008.20
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发表时间：
2008-08-01
影响因子：
6.7
通讯作者：
Park, J-Y
中科院分区：
文献类型：
--
作者：
Kim, K. A.;Park, P. W.;Park, J-Y
我们评估了CYP2C19基因型对氯吡格雷药代动力学和药效学的影响。24名受试者根据其CYP2C19基因型分为三组：纯合子广泛代谢组（homoEMs, n = 8）、杂合子EMs （heteroEMs, n = 8）和差代谢组（PMs, n = 8）。第1天给予300 mg氯吡格雷单次负荷剂量，第2天至第7天每日给予75 mg维持剂量后，我们测量了氯吡格雷的血浆水平，并评估了其抗血小板作用的药效学。PMs的平均氯吡格雷曲线下面积（AUC）分别是异质和同源样品的1.8倍和2.9倍（P = 0.013）。PMs组的平均血药浓度峰值分别是异质组和同源组的1.8倍和4.7倍（P = 0.008）。PMs的抗血小板作用明显低于异质或同源（P < 0.001）。从这些发现可以清楚地看出，CYP2C19基因型影响氯吡格雷的血浆水平并调节氯吡格雷的抗血小板作用。
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.