CYP2C19基因多态性对氯吡格雷药代动力学的影响

摘要

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.%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。