The Role of the Cytochrome P450 Polymorphisms in Clopidogrel Efficacy and Clinical Utility

Author(s): D. Tousoulis, G. Siasos, M. Zaromytidou, N. Papageorgiou, E. Stefanadi, E. Oikonomou, C. Stefanadis

Journal Name: Current Medicinal Chemistry

Volume 18 , Issue 3 , 2011

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Clopidogrel, an antiplatelet agent, prevents platelet aggregation by inhibiting the adenosine disphosphate (ADP) P2Y12 receptor, which is located on the platelet surface. Although dual antiplatelet therapy appears to be efficient, a considerable number of patients continue to experience adverse cardiovascular events, such as stent thrombosis. The percentage of low response to antiplatelet therapy varies from 4% to 30% of patients depending on the cut-off values. In addition, several factors such as poor absorption, drug-to-drug interactions, inadequate dosing, elevated body mass index, insulin resistance and the nature of acute coronary syndromes have been implicated in low clopidogrel response. Recently, studies have focused on the role of genetic polymorphisms encoding enzymes that participate in clopidogrel hepatic metabolism or receptors involved in intestinal absorption and ADP induced platelet aggregation, which may affect the percentage of platelet inhibition after clopidogrel administration. The management of clopidogrel resistance remains a controversial issue and additional studies are required to evaluate the safety and efficacy of increased loading of clopidogrel or replacement with other new antiplatelet agents such as prasugrel.

Keywords: Clopidogrel resistance, cytochrome P450, gene polymorphisms, platelets, thrombus, Clopidogrel, atherosclerosis, adenosine disphosphate, atherosclerotic disease, multifactorial pattern, cytochrome, carbon monoxide, enzymes, phospholipids, detoxification, coagulation, body mass index, polymorphisms, platelet, healthy Caucasians, coronary artery disease, erythromycin, antiplatelet therapy, percentile distribution, platelet function analyzer (PFA), vasodilator, phosphoprotein

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Article Details

Year: 2011
Page: [427 - 438]
Pages: 12
DOI: 10.2174/092986711794839151
Price: $65

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PDF: 12