Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel

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Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel.

BACKGROUND Clopidogrel is a prodrug requiring metabolism by cytochrome P450 3A (CYP3A) isoenzymes, including CYP3A5, in order to be active. It is controversial whether clopidogrel interacts with CYP3A inhibitors. We investigated the influence of CYP3A5 polymorphism on the drug interaction of clopidogrel. METHODS In phase 1 of the study, we administered clopidogrel to 16 healthy volunteers who...

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Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction.

BACKGROUND Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur. METHODS AND RESULTS The antiplatelet effect of clopidogrel was studied prospectively in 60 consecutive patients who underwent primary angioplasty (percutaneous coronary intervention [PCI]) with stenting for acute ST-segment-elevat...

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Genetic polymorphism of cytochrome P450 3A5 in Chinese.

The CYP3A subfamily enzymes are the most abundant and important drug-metabolizing enzymes. Wide variation in the CYP3A5 expression was well known. Recently, G(-44) to A of CYP3AP1 was found to segregate with CYP3A5*3 defective allele. The homozygous A(-44) subjects showed low expression of CYP3A5. In Caucasian, only 9.2% of CYP3AP1 alleles were with G(-44) and associated with the wild-type CYP3...

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Interaction of lapatinib with cytochrome P450 3A5.

Lapatinib, an oral tyrosine kinase inhibitor used for breast cancer, has been reported to cause idiosyncratic hepatotoxicity. Recently, it has been found that lapatinib forms a metabolite-inhibitor complex (MIC) with CYP3A4 via the formation of an alkylnitroso intermediate. Because CYP3A5 is highly polymorphic compared with CYP3A4 and also oxidizes lapatinib, we investigated the interactions of...

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Cytochrome P450 2C19 Polymorphism is Associated with Reduced Clopidogrel Response in Cerebrovascular Disease

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 ...

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ژورنال

عنوان ژورنال: Canadian Medical Association Journal

سال: 2006

ISSN: 0820-3946,1488-2329

DOI: 10.1503/cmaj.060044