基因多态性、药物联用和临床因素对氯吡格雷疗效的影响及相关的基因型分布  

Gene polymorphisms,drug combination and clinical factors affecting the efficacy of clopidogrel and related distributions of genotypes

作　　者：刘敏[1] 肖飞燕[1,2] 王晓飞[1] 张伟[3,2] 周淦[3,2] 

机构地区：[1]郑州大学附属郑州中心医院心血管内科 [2]中南大学临床药理研究所遗传药理学湖南省重点实验室 [3]中南大学湘雅医院临床药理研究所

出　　处：《中国临床药理学与治疗学》2015年第8期915-922,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金(81273595);863计划(2012AA02A518)

摘　　要：目的:研究可能影响氯吡格雷疗效的遗传和临床因素,提高氯吡格雷疗效,降低不良心血管事件。方法:从影响氯吡格雷药代动力学和药效学的基因多态性及其基因型分布、药物联用等方面进行研究,以半月和一年发生终点事件为观察指标。结果:此次纳入研究的药物代谢酶CYP450s、转运体、受体的基因多态性均与氯吡格雷的疗效无关。而rs7916649等位点的基因型发生终点事件的频率分布有差异,突变型个体比野生型个体发生终点事件的概率高。结论:氯吡格雷、阿司匹林、他汀类药物、β-受体阻滞剂、利尿药、质子泵抑制剂、肾素-血管紧张素系统抑制剂都对患者的愈后有影响,联合用药能提高疗效。本研究为氯吡格雷临床个体化给药提供一定的参考依据。AIM： To study the factors that may affect the efficacy of clopidogrel and enhance the efficacy, reduce adverse cardiovascular events.METHODS： The impacts of drug combination and genetic polymorphisms and genotype distributtion which influence clopidogrel ＇s pharmacokinetics and pharmacodynamics,endpoint events occurred in half of month and a year as outcome measures were stndied. RESULTS： It was found that the drug-metabolizing enzymes CYP450 s,transporter,receptor gene polymorphisms which we studied this time were not related to the efficacy of clopidogrel. But the frequency of rs7916649 alleles＇ genotype distribution of endpoint events exist differences,as to the wild-type individual,mutant genotype individuals have higher probability of endpoint events occurred. CONCLUSION： Clopidogrel,aspirin,statins,β- blockers,diuretics,proton pump inhibitors and renin- angiotensin system inhibitors do all influence patients＇ recovery,combination therapy can improve the efficacy of these drugs. The study provides reference for clinical individualized dosing of clopidogrel.

关 键 词：氯吡格雷 冠心病 基因多态性 基因型分布 药物联用 

分 类 号：R972[医药卫生—药品]