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1. The disposition and metabolic fate of ropinirole, a novel compound indicated for the symptomatic treatment of Parkinson's disease, was studied in the mouse, rat, cynomolgus monkey and man, following oral and intravenous administration of ropinirole hydrochloride. 2. In all species, nearly all...
1. Studies using human liver microsomes and recombinant human cytochrome P450 (P450) enzymes and flavin-containing monooxygenase (FMO) were performed to identify the enzymes responsible for the formation of zotepine metabolites in man. 2. Human liver microsomes produced four metabolites and a...
1. Effects of arachidonic acid, prostaglandins, retinol, retinoic acid and cholecalciferol on xenobiotic oxidations catalysed by 12 recombinant human cytochrome P450 (P450 or CYP) enzymes and by human liver microsomes have been investigated. 2. Arachidonic acid (50 μ M) significantly inhibited...
1. Pharmacokinetics were studied in mouse, rat, rabbit, dog and man after single intravenous and or oral doses of sildenafil or ( 14 C)-sildenafil (Viagra™). 2. In man, absorption from the gastrointestinal tract was essentially complete. With the exception of male rat, T max occurred at ∼ 1h...
1. A plasmid containing 1 kb of the CYP3A4 regulatory (promoter) region coupled to a reporter gene for secretary placental alkaline phosphatase (SPAP) was transfected into HepG2 cells. Transfected cells were dosed with several known inducers of CYP3A4 and the levels of SPAP were measured. The...
1. The degradation of recombinant human insulin-like growth factor-I (rhIGF-I) by purified lysosomes of rat kidney was examined in vitro . The peptide structures of the 13 degradation products were deduced from the sequence analysis and the molecular mass. Rat kidney lysosomal cathepsins...
1. Cytochrome P450 (P450) isoforms responsible for the N-deethylation and cyclohexane-hydroxylation of (±)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2- hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21) have been identified in rat and man. 2. Anti-CYP2C11 antibody...
1. The metabolism of loxtidine (1-methyl-5-(3-(3-((1-piperidinyl) methyl) phenoxy) propyl) amino-1H-1,2,4-triazole-3-methanol) was studied in freshly isolated rat, dog and human hepatocytes. Metabolism in vitro was comparable with previously available in vivo data in all three species with the...
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