质子泵抑制剂与氯吡格雷药物相互作用研究进展

Research progress in drug interaction between proton-pump inhibitors and clopidogrel

对2010年Mdeline收载的关于质子泵抑制剂(PPIs)与氯吡格雷相互作用的研究文献进行综述分析,PPIs对氯吡格雷抗血小板聚集活性的影响与多个因素相关:氯吡格雷和阿司匹林合用时,PPIs与氯吡格雷之间无临床意义的药物相互作用;当单用氯吡格雷抗血小板聚集时,PPIs对其药效的影响显著,而且不同的PPIs之间的作用强度有差异;以微观指标(如ADP或花生四烯酸诱导的血小板聚集度)为标准,则氯吡格雷和PPIs之间存在不良药物相互作用,但以宏观指标(如一级事件发生率)为标准则无临床意义的不良药物相互作用;PPIs对氯吡格雷的影响与CYP2C19基因多态性有关:快代谢型患者PPIs对氯吡格雷的抗血小板聚集作用影响显著,慢代谢型无明显影响;与单用氯吡格雷相比,PPI+阿司匹林可以显著降低胃肠道出血事件,对心血管系统没有不良影响。因此,对于PCI术后短期内行氯吡格雷和阿司匹林双抗血小板聚集患者,临床可以根据情况选择任何一个PPIs;对于单用氯吡格雷抗血小板聚集的患者,应该首选与泮托拉唑合用;PPIs合用阿司匹林能有效抗血小板聚集,而且显著减少胃肠道出血事件,因此在必须应用PPIs的情况下,阿司匹林是氯吡格雷的一个有效替代药物。

To provide references for clinical practice in the drug interaction of PPIs and clopidogrel,the literature published in 2010 from Medline was reviewed.The key words ＂PPI＋clopidogrel＂,or ＂omeprazole＋clopidogrel＂,or ＂esomeprazole＋clopidogrel＂,or ＂lansoprazole＋clopidogrel＂,or ＂rabeprazole＋clopidogrel＂,or ＂pantoprazole＋clopidogrel＂ were applied to search all of the related articles or Meta analyses.Effects of PPIs on clopidogrel anti-platelet aggregation are determined by multiple factors.When co-administrated with aspirin,clopidogrel has no clinically significant drug interaction with PPIs;when solely used,clopidogrel anti-platelet aggregation could be markedly reduced by different PPI with different strength;when taking micro-parameters（such as ADP-or arachidonic acid-induced platelet aggregation） as comparing standard,clopidogrel has adverse drug interaction with PPIs;however,when comparing macro-parameters（such as primary event incidence）,no clinically significant drug interaction exists between clopidogrel and PPIs.Effects of PPIs on clopidogrel anti-platelet aggregation ability relate to CYP2C19 polymorphism.PPI exerted stronger effects on clopidogrel in CYP2C19 rapid metabolizer than in poor metabolizer.Compared with clopidogrel,aspirin co-administrated with clopidogrel can reduce the events of gastrointestinal bleeding and has no adverse effects on cardiovascular system.In patients treated with both clopidogrel and aspirin after PCI operations,anyone of the five PPIs can be selected without adverse drug interaction.When clopidogrel solely used to anti-platelet,pantoprazole should be the first choice as its adverse effects on clopidogrel is the weakest.Aspirin can effectively exert an anti-platelet effect and markedly reduce the gastrointestinal bleeding events when co-administrated with PPIs,so that aspirin is an alternative for clopidogrel when concomitant use with PPIs.