CYP2C19基因多态性对氯吡格雷药代动力学的影响

Effect of genetic polymorphism of CYP2C19 on pharmacokinetics of clopidogrel

目的：探讨 CYP2C19基因多态性对氯吡格雷人体药动学的影响。方法29名汉族健康受试者在单次服用75 mg 氯吡格雷片后定时采血,用液质联用技术（LC-MS/ MS）分析受试者氯吡格雷血药浓度,采用 PCR-限制性片段长度多态性分析法检测 CYP2C19＊2/＊3基因突变。结果 CYP2C19＊1/＊1、CYP2C19＊1/＊2和CYP2C19＊2/＊2（＊3）3种基因型分别为9例、16例和4例。曲线下面积 AUC0-24和 AUC0-∞在三种基因型间比较差异有统计学意义（P 〈0．05）,其他药动学参数未见统计学意义（P 〉0．05）。结论口服氯吡格雷后,CYP2C19不同基因型曲线下面积不同。

Objective To investigate the effect of CYP2C19 genetic polymorphism on the pharmacokinetics of clo-pidogrel in healthy subjects. Methods A total of 29 unrelated healthy Han subjects were enrolled, and each of them re-ceived a single dose of 75 mg clopidogrel tablet. Multiple blood samples were collected and the plasma concentrations of clopidogrel were determined by a validated liquid chromatography/ tandem mass spectrometry （LC-MS/ MS）. PCR-restric-tion fragment length polymorphism （RFLP） analysis was performed to detect the CYP2C19＊2 and ＊3 gene mutations. Results The number of inviduals carrying CYP2C19＊1 / ＊1, CYP2C19＊1 / ＊2 and CYP2C19＊2 / ＊2 （＊3） were 9, 16 and 4 respectively. There were significant differences in the various genotype groups of AUC0-24 and AUC0-∞ （area under curve） （P〈0. 05）. There were no significont differences in other pharmacokinetic parameters（P 〉 0. 05）. Conclu-sions After taken clopidogrel, CYP2C19＊2（＊3） polymorphisms has effect on the AUC of clopidogrel.