Uppsala Clinical Research Centre, University Hospital, Uppsala SE 75185, Sweden.
Eur Heart J. 2009 Aug;30(16):1964-77. doi: 10.1093/eurheartj/ehp296. Epub 2009 Jul 24.
Currently, clopidogrel is recommended for treatment of patients with acute coronary syndrome and/or percutaneous coronary intervention. However, the delayed onset of the effect and the occurrence of poor platelet inhibition responders with clopidogrel as well as non-compliance to dual antiplatelet treatment are associated with a raised risk of stent thrombosis. The molecular target of the active metabolite of clopidogrel and several emerging antiplatelet treatments is the P2Y(12) receptor, which is the main platelet receptor responsible for ADP-induced platelet aggregation. Active metabolites of the thienopyridine prodrugs (ticlopidine, clopidogrel, and prasugrel) covalently bind to the P2Y(12) receptor and are irreversible, indirect platelet inhibitors. The newer, direct-acting P2Y(12) inhibitors (cangrelor and ticagrelor) change the conformation of the P2Y(12) receptor, resulting in reversible, concentration dependent inhibition of the receptor. An understanding of the similarities and differences in the properties and mechanisms of action of these new inhibitors compared with clopidogrel is needed in order to optimize the development and use of these agents in clinical practice. The objectives of this systematic review are to summarize the pharmacokinetics, pharmacodynamics, and pharmacogenetics of the different P2Y(12) inhibitors and to discuss the clinical implications for treatment of patients.
目前，氯吡格雷被推荐用于治疗急性冠脉综合征和/或经皮冠状动脉介入治疗的患者。然而，氯吡格雷作用起效时间延迟、血小板抑制反应不佳以及双联抗血小板治疗不依从与支架血栓形成风险增加相关。氯吡格雷的活性代谢物和几种新兴抗血小板治疗的分子靶点是 P2Y(12)受体，它是负责 ADP 诱导的血小板聚集的主要血小板受体。噻吩吡啶前药（噻氯匹定、氯吡格雷和普拉格雷）的活性代谢物与 P2Y(12)受体共价结合，是不可逆的、间接的血小板抑制剂。较新的、直接作用的 P2Y(12)抑制剂（坎格雷洛和替格瑞洛）改变 P2Y(12)受体的构象，导致受体的可逆、浓度依赖性抑制。为了优化这些药物在临床实践中的开发和使用，需要了解这些新抑制剂与氯吡格雷在性质和作用机制方面的异同。本系统评价的目的是总结不同 P2Y(12)抑制剂的药代动力学、药效学和药物遗传学，并讨论其对患者治疗的临床意义。
