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Int J Environ Res Public Health. 2017 Mar 14;14(3). pii: E301. doi: 10.3390/ijerph14030301.

Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel: Evidences and Perspectives.

Zhang YJ1,2, Li MP3,4, Tang J5,6, Chen XP7,8.

Author information

1
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. zhangyj287112687@163.com.
2
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. zhangyj287112687@163.com.
3
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. elskesunny@163.com.
4
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. elskesunny@163.com.
5
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. jietang@csu.edu.cn.
6
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. jietang@csu.edu.cn.
7
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. chenxp74@hotmail.com.
8
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. chenxp74@hotmail.com.

Abstract

Clopidogrel has significantly reduced the incidence of recurrent atherothrombotic events in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). However, recurrence events still remain, which may be partly due to inadequate platelet inhibition by standard clopidogrel therapy. Genetic polymorphisms involved in clopidogrel's absorption, metabolism, and the P2Y12 receptor may interfere with its antiplatelet activity. Recent evidence indicated that epigenetic modification may also affect clopidogrel response. In addition, non-genetic factors such as demographics, disease complications, and drug-drug interactions can impair the antiplatelet effect of clopidogrel. The identification of factors contributing to the variation in clopidogrel response is needed to improve platelet inhibition and to reduce risk for cardiovascular events. This review encompasses the most recent updates on factors influencing pharmacokinetic and pharmacodynamic responses to clopidogrel.

KEYWORDS:

clopidogrel; epigenetics; genetic polymorphisms; non-genetic factors; pharmacogenomics

PMID:
28335443
PMCID:
PMC5369137
DOI:
10.3390/ijerph14030301
[Indexed for MEDLINE]
Free PMC Article

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