氯吡格雷和质子泵抑制剂相互作用.docVIP

氯吡格雷和质子泵抑制剂相互作用 　　摘 要 氯吡格雷能够降低冠心病患者再次发生心肌梗死的风险，故广泛用于急性冠脉综合征和经皮冠脉介入术后的患者。临床相关指南建议，氯吡格雷应与质子泵抑制剂（proton pump inhibitor， PPI）合用以减少氯吡格雷的胃肠道不良反应。但是，氯吡格雷需经肝脏细胞色素P450酶的同功酶CYP 2C19代谢才能转化为活性产物发挥作用，而PPI同样主要由CYP 2C19代谢。药代动力学研究显示，氯吡格雷与奥美拉唑合用会发生药物相互作用、由此降低氯吡格雷的抗血小板作用，而泮托拉唑与氯吡格雷的相互作用不明显。发表于2009年的系列回顾性病例对照研究表明，氯吡格雷与PPI合用会增加心血管不良事件的发生风险。但这一研究结果并未得到前瞻性的随机、对照研究和荟萃分析的证实。因此，目前仍需进行大规模的前瞻性的随机、对照试验来分析氯吡格雷和PPI合用与心血管不良事件风险间的相关性。鉴于临床上有大量服用氯吡格雷的患者需合用PPI来降低胃肠道出血风险，建议现最好选用与氯吡格雷相互作用较小的泮托拉唑。 关键词 质子泵抑制剂 氯吡格雷 药物相互作用 中图分类号：R969.2； R973.2 文献标识码：A 文章编号：1006-1533（2013）21-0016-04 Interaction of clopidogrel and proton pump inhibitors JIANG Weiru*， ZHONG Liang （Department of Gastroenterology， Huashan Hospital， Fudan University， Shanghai 200040， China） Abstract Clopidogrel is considered as a standard medical treatment for acute coronary syndrome and patients having percutaneous coronary intervention in order to reduce the risk of new ischemic events. Combination of clopidogrel with proton pump inhibitor （PPI） is recommended by clinical guidelines in order to prevent gastrointestinal side effects. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme 2C19 and PPI are extensively metabolized by the same isoenzyme as well. Pharmacodynamic studies showed that a potential clopidogrel-PPI interaction occurred， resulting in a significant decrease of the clopidogrel platelet antiaggregation effect in case of combination of clopidogrel with omeprazole， but not with pantoprazole. A series of retrospective case-control studies published in 2009 reported that combination of clopidogrel with PPI could increase the risk of adverse cardiovascular events. However， the result of this study has not been confirmed by prospectively randomized and controlled studies and meta-analysis. So， a large-scale prospectively randomized and controlled trial should be performed in order to analyze the risk of cardiovascular adverse events associated with the combination of clopidog