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Clinical Pharmacokinetics and Pharmacodynamics of Clopidogrel

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Abstract

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 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, 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.

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Acknowledgments

This work was supported in part by the National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS) Clinical and Translational Science Award to the University of Florida (UL1 TR000064). Xi-Ling Jiang, Snehal Samant, Lawrence J. Lesko and Stephan Schmidt have no potential conflicts of interest that might be relevant to the content of this review.

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  1. Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, University of Florida at Lake Nona (Orlando), 6550 Sanger Road, Room 467, Orlando, FL, 32827, USA

    Xi-Ling Jiang, Snehal Samant, Lawrence J. Lesko & Stephan Schmidt

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  1. Xi-Ling Jiang
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  2. Snehal Samant
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Correspondence to Stephan Schmidt.

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Jiang, XL., Samant, S., Lesko, L.J. et al. Clinical Pharmacokinetics and Pharmacodynamics of Clopidogrel. Clin Pharmacokinet 54, 147–166 (2015). https://doi.org/10.1007/s40262-014-0230-6

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