Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel: Evidences and Perspectives.
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.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. zhangyj287112687@163.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. zhangyj287112687@163.com.
Yan-Jiao
YJ
Zhang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. elskesunny@163.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. elskesunny@163.com.
Mu-Peng
MP
Li
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. jietang@csu.edu.cn.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. jietang@csu.edu.cn.
Jie
J
Tang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. chenxp74@hotmail.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. chenxp74@hotmail.com.
Xiao-Ping
XP
Chen
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000077144:Clopidogrel; D015897:Comorbidity; D004347:Drug Interactions; D006801:Humans; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D012720:Severity of Illness Index; D012959:Socioeconomic Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D016896:Treatment Outcome
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine
clopidogrel; epigenetics; genetic polymorphisms; non-genetic factors; pharmacogenomics