AIM Carriers of the reduced-function CYP2C19 allele receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel exhibit diminished platelet inhibition and an increased risk of events. The purpose of this study was to investigate the effects of CYP2C19 gene variants on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing elective percutaneous cor...

Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas poor metabolizers have increased trough concentrations and are at increased risk o...

Background-—The role of the CYP2C19 genotype on clopidogrel efficacy has been studied widely, with data suggesting reduced clopidogrel efficacy in loss-of-function variant carriers taking clopidogrel after percutaneous coronary intervention; however, data are limited regarding the association between CYP2C19 genetic variants and outcomes in stroke patients. We investigated whether CYP2C19 metab...

CONTEXT The US Food and Drug Administration recently recommended that CYP2C19 genotyping be considered prior to prescribing clopidogrel, but the American Heart Association and American College of Cardiologists have argued evidence is insufficient to support CYP2C19 genotype testing. OBJECTIVE To appraise evidence on the association of CYP2C19 genotype and clopidogrel response through systemat...

OBJECTIVES Voriconazole, a first-line agent for the treatment of invasive fungal infections (IFIs), is metabolized by CYP2C19. A significant proportion of patients fail to achieve therapeutic trough concentrations with standard weight-based voriconazole dosing, placing them at increased risk for treatment failure, which can be life threatening. We sought to test the association between the CYP2...

PURPOSE This research investigated the biotransformation of thalidomide by cytochrome P-450 (CYP). EXPERIMENTAL DESIGN We used liver microsomes from humans and/or animals and the recombinant specific CYP isozymes to investigate CYP-mediated metabolism of thalidomide. RESULTS Thalidomide was biotransformed into 5-hydroxythalidomide (5-OH) and diastereomeric 5'-hydroxythalidomide (5'-OH) by l...

BACKGROUND CYP2C19 encodes a member of the cytochrome P450 superfamily of enzymes, which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of cancer. In the past decade, two common polymorphisms among CYP2C19 (CYP2C19*2 and CYP2C19*3) that are responsible for the poor metabolizers (PMs) phenotype in humans and c...

The capacity of clopidogrel to inhibit ADP-induced platelet aggregation shows wide intersubject variability. To determine whether frequent functional variants of genes coding for candidate cytochrome P450 (CYP) isoenzymes involved in clopidogrel metabolic activation (CYP2C19*2, CYP2B6*5, CYP1A2*1F, and CYP3A5*3 variants) influence the platelet responsiveness to clopidogrel, we conducted a prosp...

We have identified CYP2C19 and CYP3A4 as the principal cytochrome P450s involved in the metabolism of flunitrazepam to its major metabolites desmethylflunitrazepam and 3-hydroxyflunitrazepam. Human CYP2C19 and CYP3A4 mediated the formation of desmethylflunitrazepam with Km values of 11.1 and 108 microM, respectively, and 3-hydroxyflunitrazepam with Km values of 642 and 34.0 microM, respectively...

Laboratories are increasingly requested to perform CYP2C19 genetic testing when managing clopidogrel therapy, especially in patients with acute coronary syndrome undergoing percutaneous coronary intervention. To ensure high quality molecular testing and ascertain that the referring clinician has the correct information for CYP2C19 genotype-directed antiplatelet therapy, a proficiency testing sc...