DMD 19646 Role of Flavin-containing Monooxygenase in Oxidative Metabolism of Voriconazole by Human Liver Microsomes
نویسندگان
چکیده
Division of Molecular Pharmaceutics, School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC USA (SBY, AB, YG, DRT) Laboratory for Pharmacotechnology and Biopharmacy, Katholieke Universiteit Leuven, O&N2, Herestraat 49-Box 921, 3000 Leuven, Belgium (PPA; PA) Department of Pediatrics, Duke Clinical Research Institute, Duke University, Durham, NC, USA (DKB) DMD Fast Forward. Published on March 24, 2008 as doi:10.1124/dmd.107.019646
منابع مشابه
Role of flavin-containing monooxygenase in oxidative metabolism of voriconazole by human liver microsomes.
Voriconazole is a potent second-generation triazole antifungal agent with broad-spectrum activity against clinically important fungi. It is cleared predominantly via metabolism in all species tested including humans. N-Oxidation of the fluoropyrimidine ring, its hydroxylation, and hydroxylation of the adjacent methyl group are the known pathways of voriconazole oxidative metabolism, with the N-...
متن کاملSpecies Differences in the Oxidative Desulfurization of a Thiouracil-Based Irreversible Myeloperoxidase Inactivator by Flavin-Containing Monooxygenase Enzymes.
N1-Substituted-6-arylthiouracils, represented by compound 1 [6-(2,4-dimethoxyphenyl)-1-(2-hydroxyethyl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one], are a novel class of selective irreversible inhibitors of human myeloperoxidase. The present account is a summary of our in vitro studies on the facile oxidative desulfurization in compound 1 to a cyclic ether metabolite M1 [5-(2,4-dimethoxyphenyl)-2,...
متن کاملExtrahepatic metabolism of carbamate and organophosphate thioether compounds by the flavin-containing monooxygenase and cytochrome P450 systems.
The cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes are the major oxidative enzymes in phase I metabolism. Many organophosphate and carbamate thioether compounds are excellent substrates for these enzymes. Stereoselective sulfoxidation of fenthion and methiocarb by human liver, kidney, and microsomes was investigated. A high level of stereoselectivity in the formation o...
متن کاملShort Communication EXTRAHEPATIC METABOLISM OF CARBAMATE AND ORGANOPHOSPHATE THIOETHER COMPOUNDS BY THE FLAVIN-CONTAINING MONOOXYGENASE AND CYTOCHROME P450 SYSTEMS
The cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes are the major oxidative enzymes in phase I metabolism. Many organophosphate and carbamate thioether compounds are excellent substrates for these enzymes. Stereoselective sulfoxidation of fenthion and methiocarb by human liver, kidney, and microsomes was investigated. A high level of stereoselectivity in the formation o...
متن کاملShort Communication EXTRAHEPATIC METABOLISM OF CARBAMATE AND ORGANOPHOSPHATE THIOETHER COMPOUNDS BY THE FLAVIN-CONTAINING MONOOXYGENASE AND CYTOCHROME P450 SYSTEMS
The cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes are the major oxidative enzymes in phase I metabolism. Many organophosphate and carbamate thioether compounds are excellent substrates for these enzymes. Stereoselective sulfoxidation of fenthion and methiocarb by human liver, kidney, and microsomes was investigated. A high level of stereoselectivity in the formation o...
متن کامل