RESUMO
The disposition of quinfamide 1-(dichloroacetyl)-6-(2-furoyloxy)-1, 2, 3, 4-tetrahydroquinoline, an enteric anti-amoebic agent, was studied in the rat. A peak blood level equivalent to 2.3 micrograms/ml of quinfamide was observed at 7 hr following a 20 mg/kg oral dose. Urinary recovery of radioactivity was much higher (84%) following intravenous than oral (48%) administration. Drug levels, in all of the tissues examined. were low. The major pathways of quinfamide metabolism in the rat involve hydrolysis of one or both ester groups, acetylation of the de-acylated product to 1-acetyl-1, 2, 3, 4-tetrahydro-6-quinolinol, oxidation of this to the 1-glycolyl metabolite, and aromatization to 6-hydroxyquinoline.
Assuntos
Quinolinas/metabolismo , Animais , Biotransformação , Fezes/análise , Absorção Intestinal , Masculino , Ratos , Ratos Endogâmicos , Distribuição TecidualRESUMO
The biotransformation of 14C-amrinone was studied in rats, dogs, and monkeys by automated gradient high-performance liquid chromatography. The major pathways of metabolism elucidated are: A) glucuronidation at the primary amino nitrogen atom and/or the enolized oxygen atom of the pyridone ring; B) addition of glutathione at the pyridone 2-position and ultimate hydrolysis of this compound to the 2-S-cysteinyl metabolite; C) formation of the primary amino N-acetyl derivative and subsequent oxidation of this to the corresponding N-glycolate. In each species studied, urine was the primary route of elimination and unchanged amrinone was the major urinary excretion product, the other known pathways being: rat, A and C; dog, A and B; monkey, A.
Assuntos
Aminopiridinas/metabolismo , Cardiotônicos/metabolismo , Administração Oral , Aminopiridinas/administração & dosagem , Amrinona , Animais , Cardiotônicos/administração & dosagem , Cromatografia Líquida de Alta Pressão , Cães , Feminino , Glucuronatos/urina , Glicolatos/urina , Inativação Metabólica , Macaca mulatta , Ratos , Ratos EndogâmicosRESUMO
The metabolism of trilostane, a novel inhibitor of adrenal steroidogenesis, was studied in the rat and monkey. In the rat, a peak blood level, equivalent to 2 microgram/ml of trilostane, was observed following a 25 mg/kg oral dose; excretion was mainly via the feces. In the monkey, the peak plasma level, equivalent to 15 microgram/ml, was observed 2 hr after a 20 mg/kg oral dose; elimination of radioactivity was predominantly in the urine. The five major metabolites of trilostane in monkey urine have been isolated and partially characterized. The primary metabolic pathways involved hydroxylation and glucuronide formation.
Assuntos
Androstanóis/metabolismo , Di-Hidrotestosterona/análogos & derivados , Animais , Biotransformação , Feminino , Haplorrinos , Absorção Intestinal , Macaca mulatta , Masculino , Nitrilas/metabolismo , Oxirredução , Ratos , Especificidade da Espécie , Fatores de Tempo , Distribuição TecidualRESUMO
A gas chromatograph-mass fragmentography method for simultaneous assay of 17-monochloroacetyl-ajmaline (MCAA) and its hydrolysis product, ajmaline, is described. Recovery of both compounds from whole blood averaged 71%. About 5% of MCAA was hydrolyzed during the assay procedure. The method was accurate and precise to within a few percent. It was suitable for assays of blood levels in the dog after an i.v. dose of 2 mg/kg or an oral dose of 5 mg/kg.
