PURPOSE Clopidogrel is a prodrug that requires transformation into an active metabolite by cytochrome P450 (CYP) in the liver in order to irreversibly inhibit the P2Y12 adenosine diphosphate platelet receptor. CYP2C19 polymorphism has been reported to correlate with reduced antiplatelet activity of clopidogrel in coronary artery disease. We assessed the association between CYP2C19 polymorphism ...

Clopidogrel is the new useful drug that is widely used at present (1). Clopidogrel is a thienopyridine (1). This drug mainly affects platelets by “irreversibly inhibiting platelet aggregation by selectively binding to adenylate cyclase-coupled ADP receptors on the platelet surface” (1). At present clopidogrel is indicated for the “prevention of ischemic stroke, myocardial infarction, and vascul...

Clopidogrel is an antiplatelet prodrug that is recommended to reduce the risk of recurrent thrombosis in coronary artery disease (CAD) patients. Paraoxonase 1 (PON1) is suggested to be a rate-limiting enzyme in the conversion of 2-oxo-clopidogrel to active thiol metabolite with inconsistent results. Here, we sought to determine the associations of CYP2C19 and PON1 gene polymorphisms with clopid...

The antiplatelet drug clopidogrel is metabolized to an acyl-β-d-glucuronide, which causes time-dependent inactivation of CYP2C8. Our aim was to characterize the UDP-glucuronosyltransferase (UGT) enzymes that are responsible for the formation of clopidogrel acyl-β-d-glucuronide. Kinetic analyses and targeted inhibition experiments were performed using pooled human liver and intestine microsomes ...

While acute myocardial infarction (MI) is associated with impaired clopidogrel responsiveness, systematic evaluation is lacking due to the inability of functional aggregation-based assays to analyse clopidogrel responsiveness in the presence of glycoprotein IIb/IIIa inhibitors. Using the P2Y12-specific, non-aggregation-based platelet-reactivity-index (PRI) we assessed clopidogrel responsiveness...

Dasabuvir, a nonnucleoside NS5B polymerase inhibitor, is a sensitive substrate of cytochrome P450 (CYP) 2C8 with a potential for drug-drug interaction (DDI) with clopidogrel. A physiologically based pharmacokinetic (PBPK) model was developed for dasabuvir to evaluate the DDI potential with clopidogrel, the acyl-β-D glucuronide metabolite of which has been reported as a strong mechanism-based in...

CLOPIDOGREL BLOCKS THE platelet P2Y12 adenosine diphosphate (ADP) receptor, inhibition of which has been shown to reduce cardiovascular events in patients with an acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). Although the standard 75-mg daily maintenance dose of clopidogrel has proven to be clinically efficacious in these settings, variability i...

OBJECTIVES The purpose of this study was to characterize clopidogrel hypersensitivity and describe its successful management with oral steroids without clopidogrel discontinuation. BACKGROUND Hypersensitivity reactions to clopidogrel are poorly understood and present difficulty in management. METHODS Patients diagnosed with clopidogrel hypersensitivity after percutaneous coronary interventi...

OBJECTIVES This study sought to determine the incidence of aspirin nonresponsiveness in addition to clopidogrel nonresponsiveness and whether this association identifies patients at an increased risk of drug-eluting stent (DES) thrombosis. BACKGROUND Nonresponsiveness to clopidogrel is a predictor of DES thrombosis. No prospective data exist about the possible association of dual nonresponsiv...

BACKGROUND Several studies have suggested that proton-pump inhibitors (PPIs), mostly omeprazole, interact with clopidogrel efficacy by inhibiting the formation of its active metabolite via CYP2C19 inhibition. Whether this occurs with all PPIs is a matter of debate. As rabeprazole is a less potent CYP2C19 inhibitor than other PPIs, we studied the interaction between rabeprazole and the antiplate...