ABSTRACT
Carpipramine administered orally is excreted via the urine and faeces in rat, rabbit, dog and man. Many metabolites are formed, including several conjugates in the urine. A total of 20-25 metabolites was detected by t.l.c. and h.p.l.c., 16 of which were isolated and identified. Three metabolic pathways were observed: hydroxylation of the iminodibenzyl ring to a phenol or alcohol without modification of the side-chain, hydroxylation of the terminal piperidine of the 2-piperidinol side-chain, and cyclization and dehydrogenation of the same 2-piperidinol group.
Subject(s)
Anti-Anxiety Agents , Benzodiazepines , Dibenzazepines/metabolism , Dogs/metabolism , Rabbits/metabolism , Rats, Inbred Strains/metabolism , Animals , Biotransformation , Chromatography, High Pressure Liquid , Feces/analysis , Female , Humans , Hydroxylation , Magnetic Resonance Spectroscopy , Male , Mass Spectrometry , Molecular Conformation , Rats , Species Specificity , Spectrophotometry, Infrared , Urine/analysisABSTRACT
4-Methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (35 972 R.P., oltipraz) and its metabolites were extracted from human urine and from mouse, rat and monkey urine using Amberlite XAD4 resin. The metabolites were identified by GLC, TLC and HPLC and isolated by preparative TLC or HPLC. The structures of 11 compounds were determined by spectroscopic examination (MS, IR, NMR). Six of the principal metabolites isolated in sufficient quantity from human urine were administered to the mouse, confirming the metabolic pathways of oltipraz.
