BMS-823778 is a potent and selective inhibitor of 11β-HSD1, an enzyme that regulates tissue-specific intracellular glucocorticoid metabolism and is a compelling target for the treatment of metabolic diseases. Metabolism of BMS-823778 was mediated mainly by polymorphic CYP2C19, with minor contributions from CYP3A4/5 and UGT1A4. The clinical pharmacokinetics (PK) of BMS-823778 was first investiga...

Hepatocellular carcinoma (HCC), one of the most dangerous malignancies with an increasing incidence and a high mortality rate, represents a major international health problem. HCC progression is known to involve genome-wide alteration of epigenetic modifications, leading to aberrant gene expression patterns. The activity of CYP2C19, an important member of the cytochrome P450 superfamily, was re...

A conformationally targeted anti-peptide antibody was produced by immunizing a rabbit with a cyclized peptide corresponding to a loop region of human CYP2C19 (residues 250-261). In an enzyme-linked immunosorbent assay, the antibody bound strongly to recombinant CYP2C19 and poorly to recombinant CYP2C8, CYP2C9, and CYP2C18. In immunoblotting studies, the antibody bound strongly to recombinant CY...

(-)-N-3-Benzyl-phenobarbital (NBPB) was reported to be a potent and selective inhibitor of CYP2C19. To validate the selectivity of NBPB toward CYP2C19 in human liver microsomes, the inhibitory effects on major cytochrome P450 isoform-specific reactions were evaluated in the present study. In human liver microsomes, NBPB showed potent competitive inhibition on CYP2C19-mediated S-mephenytoin 4'-h...

The capacity of clopidogrel to inhibit ADPinduced platelet aggregation shows wide intersubjectvariability.Todeterminewhether 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 prospectiv...

Clopidogrel is the thienopyridine of choice for prevention of ischemic events and stent thrombosis in patients with atherotrombotic disease. Recent studies suggest that certain genetic variants involving CYP450 system are responsible for wide interindividual variability in treatment response profiles among clopidogrel treated individuals. The aim of this study was to define the prevalence of mo...

BACKGROUND Compared with non-reversible, indirect P2Y12 inhibitor clopidogrel, ticagrelor is a reversible, direct acting inhibitor. The CYP2C19*2 allele is a common genetic variant in individuals that need given higher clopidogrel in acute coronary syndrome patients. OBJECTIVE We aimed to assess a pharmacogenetic approach of doubling dose clopidogrel compare with standard dose of ticagrelor a...

AIM The aim of this study was to determine the impact of CYP2C19 and ABCB1 gene polymorphisms and CYP3A4 isoenzyme activity on stent implantation complications among patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). PATIENTS AND METHODS Seventy-six patients (median age 63, range 37-91 years) with an ACS who underwent PCI were screened for C...

Voriconazole is a triazole antifungal agent with potent activity against a broad spectrum of clinically significant pathogens. In vivo and in vitro studies have demonstrated that voriconazole is extensively metabolized, with the major circulating metabolite resulting from N-oxidation. In the present study, we report on the human cytochrome P450 enzymes responsible for the generation of this met...