摘要
目的:研究细胞色素代谢酶CYP2C9和CYP2C19基因多态性对中国健康人口服氯吡格雷后药效动力学的影响。方法:24例健康男性受试者单剂量空腹口服氯吡格雷150 mg。用TaqMan探针方法进行CYP2C9和CYP2C19基因分型。测定药前和药后2,5,10,24和48 h血小板聚集率。结果:24例健康受试者空腹口服氯吡格雷150 mg后2 h即观察到血小板聚集率的下降,药效持续至药后48 h。Emax[MPA相对于基线的降低的百分比(IPA)的最大值]在CYP2C19*1/*1,*1/*2(or*3),*2/*3(or*2)携带者中分别为(60.3±21.0),(48.3±13.4)和(29.9±13.8),有显著性差异(P<0.05)。Emax在CYP2C9*1/*1,*1/*2(or*3)携带者中分别为(44.9±52.2)和(50.8±29.4),没有显著性差异。AUEC(IPA-时间曲线下面积)在CYP2C19*1/*1,*1/*2(or*3),*2/*3(or*2)携带者中分别为(22.8±9.8),(20.0±6.6)和(9.51±9.7),在CYP2C9*1/*1,*1/*2(or*3)携带者中分别为(20.6±19.9)和(20.8±13.7),均无显著性差异。结论:中国健人群中CYP2C19基因变异携带者氯吡格雷药效学降低。
Objective：To investigate the effects of CYP2C19 and CYP2C9 polymorphisms on the pharmacodynamics of clopidogrel in Chinese male healthy volunteers.Methods：Male volunteers（n=24） aged from 18 to 35 were orally administrated with clopidogrel tablet 150mg.Genotyping was performed for CYP2C19 and CYP2C9 on samples from healthy subjects participating in the study.Platelet aggregation was measured before and 2,5,10,24,48h after administration.Results：Antiplatelet effect was observed 2h after administration,and maintained to 48h post-dose.Emax（expressed as the maximum of IPA） of CYP2C19＊1/＊1,＊1/＊2（or ＊3）,＊2/＊3（or ＊2） carriers were（60.3±21.0）,（48.3±13.4） and（29.9±13.8）,respectively,and there was significant difference between different gene groups（P0.05）.Emax of CYP2C9＊1/＊1 and ＊1/＊2（or ＊3） carriers were（44.9±52.2） and（50.8±29.4）,respectively,and there was no significant difference between different gene groups.AUEC（area under IPA-time curve） of CYP2C19＊1/＊1,＊1/＊2（or ＊3） and ＊2/＊3（or ＊2） carriers were（22.8±9.8）,（20.0±6.6） and（9.51±9.7）,AUEC of CYP2C9＊1/＊1 and ＊1/＊2（or ＊3） carriers were（20.6±19.9） and（20.8±13.7）,respectively,and there was no significant difference between different gene groups.Conclusion：CYP2C19 genetic polymorphism is a factor causing drop in clopidogrel responsiveness in health Chinese volunteers.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2011年第13期1217-1221,共5页
Chinese Journal of New Drugs
基金
国家"重大新药创制"科技重大专项"创新药物临床研究技术平台建设"(2008ZX09312-018)
