质子泵抑制剂与氯吡格雷的药物相互作用解析.pdfVIP

中国药物应用与监测2012 年12 月第9 卷第6 期 Chinese Journal of Drug Application and Monitoring, Vol.9, No.6, December 2012 ·药学进展 · 质子泵抑制剂与氯吡格雷的药物相互作用解析 陈　洁，陈世耀，刘以梅（复旦大学附属中山医院消化科，上海 200032 ） [摘要]　近年来，临床研究发现氯吡格雷合用质子泵抑制剂（proton pump inhibitors, PPI ）可能会增加急性冠脉综合征（acute coronary syndrome, ACS ）或经皮冠状动脉介入（percutaneous coronary intervention, PCI ）术后患者心血管不良事件发生的风险， 因此，联合用药存在争议。本文从氯吡格雷与CYP2C 19 多态性、PPI 与氯吡格雷在药理及临床作用上的相互影响、相关临床 研究来深入解析药物相互作用。药代动力学研究的Meta 分析结果显示，PPI 可能削弱了氯吡格雷抗血小板的效应。10 个临 床观察性研究都体现了这个观点，但文献质量偏低，而其余3 篇低质量的观察性研究、5 篇中等质量的观察性研究和1篇高质 量的RCT 均未发现氯吡格雷合用PPI 会显著增加患者心血管不良事件的发生风险。 [关键词]　氯吡格雷；质子泵抑制剂；CYP2C19 ；相互作用 [ 中图分类号] R969.2 [文献标识码] A [文章编号] 1672 – 8157(2012)06 – 0357 – 03 Insight of drug interaction between proton pump inhibitors and clopidogrel CHEN Jie, CHEN Shi-yao, LIU Yi-mei(Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China) [ABSTRACT]　Some clinical researches showed that combination use of proton pump inhibitors (PPIs) and clopidogrel might be associated with increased risks of cardiovascular events in patients with acute coronary syndrome or after percutaneous coronary intervention. This article discussed and analyzed the controversial questions regarding clopidogrel and CYP2C 19 polymorphism, the interaction between PPIs and clopidogrel in pharmacology and clinical effect and the possible suggestions by reviewing the published studies. A meta-analysis of pharmacokinetic studies showed that PPIs might attenuate the antiplatelet effect of clopidogrel. Ten observational researches with poor quality stated that combination use of PPIs and clopidogrel might increase the risk of cardiovascular events, while three other low quality observational studies, five moderate quality observational studies and one high quality randomized controlled trial found no significant relationship between combination use of PPIs and clopidogrel and increased risks of cardiovascular ev