Clinical pharmacokinetics and pharmacodynamics of clopidogrel.
Clinical pharmacokinetics and pharmacodynamics of clopidogrel.
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DOI：
10.1007/s40262-014-0230-6
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发表时间：
2015-03
影响因子：
4.5
通讯作者：
Schmidt S
中科院分区：
文献类型：
--
作者：
Jiang XL;Samant S;Lesko LJ;Schmidt S
急性冠脉综合征(ACS)仍然是威胁生命的疾病，与高发病率和死亡率有关。阿司匹林和氯吡格雷联合抗血小板治疗可以减少急性冠脉综合征患者的心血管事件。然而，除了由于与P2Y12受体的不可逆结合而延长了血小板反应性的恢复之外，氯吡格雷治疗的反应在个体之间也有很大的差异性。治疗反应的这种高个体间变异性主要与细胞色素(CYP)2C19编码基因的遗传多态有关，这种基因多态影响氯吡格雷的药代动力学。虽然FDA已经发布了针对CYP2C19代谢不良药物的框式警告，因为这些患者的疗效可能会降低，但多变量分析的结果表明，其他因素，包括年龄、性别、肥胖、合并疾病和药物-药物相互作用，都可能导致治疗反应的总体受试者之间的差异。然而，这些因素中的每一个在多大程度上影响了总体的可变性，以及它们之间的相互关系目前尚不清楚。这篇综述文章的目的是全面介绍影响氯吡格雷的药代动力学和药效学的不同因素，以及它们如何在机制上对氯吡格雷治疗的个体差异做出贡献。
Acute coronary syndromes (ACS) remain life-threatening disorders that are associated with high morbidity and mortality. Dual-antiplatelet therapy with aspirin and clopidogrel has shown to reduce cardiovascular events in patients with ACS. However, there is substantial inter-individual variability in response to clopidogrel treatment in addition to prolonged recovery of platelet reactivity as a result of irreversible binding to P2Y12 receptors. This high inter-individual variability in treatment response has primarily been associated with genetic polymorphisms in the genes encoding for cytochrome (CYP) 2C19 that affect clopidogrel’s pharmacokinetics. While FDA has issued a boxed warning for CYP2C19 poor metabolizers due to a potentially reduced efficacy in these patients, results from multivariate analyses suggest that additional factors, including age, sex, obesity, concurrent diseases and drug-drug interactions, may all contribute to the overall between-subject variability in treatment response. However, the extent to which each of these factors contributes to the overall variability and how they are interrelated is currently unclear. The objective of this review article is to provide a comprehensive update on the different factors that influence clopidogrel’s pharmacokinetics and pharmacodynamics and how they mechanistically contribute to inter-individual differences in response to clopidogrel treatment.
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影响因子：
6.6
作者：
Bismuth-Evenzal, Yona;Gonopolsky, Yehudit;Rehavi, Moshe
通讯作者：
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通讯作者：
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4.8
作者：
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通讯作者：
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