抗血小板药物替格瑞洛药代药效动力学及遗传药理学研究进展

摘要/Abstract

摘要： 替格瑞洛是2010年批准上市的抗血小板新药,属于新型环戊基三唑嘧啶类(CPTP)口服P2Y12受体拮抗剂。替格瑞洛口服后迅速吸收,中位达峰时间约 1.5 h。与已有P2Y12受体拮抗剂氯吡格雷和普拉格雷相比,替格瑞洛具有显著优势:无需代谢激活故起效迅速;与P2Y12受体呈可逆性结合,故停药后血小板功能恢复较快。此外,替格瑞洛可以通过抑制非血小板细胞表面的P2Y12受体从而产生其他药理学作用。替格瑞洛的药动学特征不受年龄、性别、饮食以及对氯吡格雷反应性的影响。替格瑞洛主要经CYP3A4代谢,可迅速产生血药浓度依赖的血小板抑制作用,且对氯吡格雷抵抗的患者同样有效。更重要的是,替格瑞洛的抗血小板作用不受具有多态性的药物转运体(ABCB1)和代谢酶(CYP2C19)基因型的影响。本文主要概述替格瑞洛药动学、药效学以及遗传药理学方面的研究进展。

关键词: 替格瑞洛, 药动学, 药效学, 遗传药理学

Abstract: Ticagrelor is a recently approved oral antiplatelet agent that belongs to a new chemical class, the cyclopentyltriazolopyrimidines (CPTP). Ticagrelor is rapidly absorbed, with a median time to maximum concentration of 1.5 hours. The new drug possesses advantages compared with other P2Y12 receptor antagonists such as clopidogrel and prasugrel in that it acts more quickly with no necessity of metabolic activation, bonds to P2Y12 receptor reversibly and therefore the platelet function can recover rapidly after drug withdrawal. Furthermore, ticagrelor may confer additional pharmacological effect via inhibition of non-platelet P2Y12 receptors. The pharmacokinetic characteristics of ticagrelor are not influenced by age, gender, diet, or clopidogrel responsiveness. Ticagrelor is primarily metabolized by cytochrome P450 (CYP) 3A4, rapidly produces plasma concentration-dependent IPA and can overcome non-responsiveness in patients previously treated with clopidogrel. What's more, CYP2C19 and ABCB1 genotypes show no effects on the pharmacodynamic profile of ticagrelor. This review summarized recent progress in pharmacokinetics, pharmacodynamics and pharmacogenetics of ticagrelor.

Key words: ticagrelor, pharmacokinetics, pharmacodynamics, pharmacogenetics

中图分类号:

R969.1

李慕鹏, 熊艳, 陈小平. 抗血小板药物替格瑞洛药代药效动力学及遗传药理学研究进展[J]. 中国临床药理学与治疗学, 2014, 19(2): 214-222.

LI Mu-peng, XIONG Yan, CHEN Xiao-ping. Progress in pharmacokinetics, pharmacodynamics and pharmacogenetics of the antiplatelet drug ticagrelor[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(2): 214-222.

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