Clinical Pharmacokinetics and Pharmacodynamics of Clopidogrel

被引:188
作者
Jiang, Xi-Ling [1 ]
Samant, Snehal [1 ]
Lesko, Lawrence J. [1 ]
Schmidt, Stephan [1 ]
机构
[1] Univ Florida Lake Nona Orlando, Ctr Pharmacometr & Syst Pharmacol, Dept Pharmaceut, Orlando, FL 32827 USA
基金
美国国家卫生研究院;
关键词
PROTON-PUMP INHIBITORS; PERCUTANEOUS CORONARY INTERVENTION; CHRONIC KIDNEY-DISEASE; TREATMENT PLATELET REACTIVITY; CALCIUM-CHANNEL BLOCKERS; DUAL ANTIPLATELET THERAPY; GENE SEQUENCE VARIATIONS; OF-FUNCTION POLYMORPHISM; STIMULATED PHOSPHOPROTEIN INDEX; SEROTONIN REUPTAKE INHIBITORS;
D O I
10.1007/s40262-014-0230-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Acute coronary syndromes (ACS) remain life-threatening disorders, which are associated with high morbidity and mortality. Dual antiplatelet therapy with aspirin and clopidogrel has been shown to reduce cardiovascular events in patients with ACS. However, there is substantial inter-individual variability in the response to clopidogrel treatment, in addition to prolonged recovery of platelet reactivity as a result of irreversible binding to P2Y(12) receptors. This high inter-individual variability in treatment response has primarily been associated with genetic polymorphisms in the genes encoding for cytochrome (CYP) 2C19, which affect the pharmacokinetics of clopidogrel. While the US Food and Drug Administration has issued a boxed warning for CYP2C19 poor metabolizers because of 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 the pharmacokinetics and pharmacodynamics of clopidogrel and how they mechanistically contribute to inter-individual differences in the response to clopidogrel treatment.
引用
收藏
页码:147 / 166
页数:20
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