河南汉族CYP2C19基因多态性对氯吡格雷药物代谢动力学的影响

Effect of CYP2C19 genetic polymorphism on pharmacokinetics of clopidogrel

目的:探讨CYP2C19基因多态性对氯吡格雷人体药物代谢动力学的影响。方法:43名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13、24和6例。药时曲线下面积(AUC)0-24和AUC0-∞在三种基因型间比较,差异有统计学意义(P<0.05)。结论:口服氯吡格雷后,CYP2C19不同基因型AUC不同。

Aim： To determine the effect of CYP2C19 genetic polymorphism on the pharmacokinetics of clopidogrel in healthy Chinese subjects. Methods： A total of 43 unrelated healthy Han subjects were enrolled,and each of them received 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. PCR-restriction fragment length polymorphism analysis was performed to detect the CYP2C19＊ 2 and ＊ 3 gene mutations. Results： The number of the inviduals carrying CYP2C19＊ 1 / ＊ 1,CYP2C19＊ 1 / ＊ 2 and CYP2C19 ＊ 2 / ＊ 2（ ＊ 3） were 13,24 and 6,respectively.There were significant differences in the various genotype groups of AUC0-24 and AUC0-∞（ P〈0. 05）. Conclusion：CYP2C19 polymorphisms affect the AUC of clopidogrel.