细胞色素P450 2C19多态性与对氯吡格雷的反应性研究进展

Review of the Relationship between Polymorphisms of Cytochrome P450 2C19 and Clopidogrel Responsiveness

氯吡格雷是一种无活性的前体药物,进入体内后需要通过细胞色素P450(主要是细胞色素P450 2C19即CYP2C19)氧化为活性代谢物而发挥其抗血小板作用。越来越多的研究发现CYP2C19某些基因多态性(主要是细胞色素P450*2)与氯吡格雷的活性代谢产物减少,血小板抑制程度减轻,及主要不良心血管事件及支架内血栓增加有关。现就细胞色素P450多态性对氯吡格雷的药代动力学、药效动力学与临床终点事件的影响,及对细胞色素P450等位基因携带者的处理最新研究进展进行综述。

Clopidogrel is an inactive prodrug,and must be oxidized to its active metabolite by cytochrome P450 enzymes（mainly by CYP2C19） to achieve its antiplatelet effects.Patients with certain genetic variants in CYP2C19 have been found to have lower levels of the active metabolite,less platelet inhibition,and greater risk of MACE and in-stent thrombosis.This article reviews studies concerning the impacts of CYP2C19 polymorphisms on pharmacokinetics and pharmacodyanamics of clopidogrel and clinical outcomes of patients who are taking clopidogrel,and the potentially alternative strategies for carriers of genetic variants of CYP2C19.