Carpipramine metabolism in the rat, rabbit and dog and in man after oral administration.

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.

Disposition of 14C-oltipraz in animals. Pharmacokinetics in mice, rats and monkeys. Comparison of the biotransformation in the infected mouse and in the schistosomes.

14C-labelled 4-methyl-5(2-pyrazinyl)-1,2-dithiole-3-thione (14C-oltipraz, 35 972 R.P.) was orally administered to rhesus monkeys (20 mg/kg), rats (50 mg/kg) and female mice infected with Schistosoma mansoni (100 and 250 mg/kg). The absorption of oltipraz varied with the animal species and the dose administered. In each species, the pharmacokinetics of oltipraz in the plasma and red blood cells were generally similar. 40 to 57% of the radioactive dose was excreted in urine, depending on the animal species and dose levels. In the mouse, there was negligible elimination of radioactivity as 14CO2. Whole-body autoradiographic studies in mice showed that, during the first 24 h, radioactivity was present mainly in the gastro-intestinal tract, bile, urine, liver and kidneys. In the male and female worms, the nature and amounts of radioactive products present differed.

Comparison of the metabolism of oltipraz in the mouse, rat and monkey and in man. Distribution of the metabolites in each species.

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.

[Study of serum concentrations and urinary excretion of secnidazole after oral administration in man. Comparison with tinidazole]. / Etude des taux sériques et de l'élimination urinaire du secnidazole après administration orale chez l'homme. Comparaison avec le tinidazole.

Secnidazole, a derivative of 5-nitro imidazole exhibits trichomonacid, amoebicid and antimicrobial properties; it has been studied in view of its biological fate in healthy volunteers (man and woman) comparatively with tinidazole. Both products were administered orally to the same volunteers at the single dose level of 2 g. The seric concentrations and the pharmacokinetic profile were determined up to the 72nd hour after drug administration. The whole urinary excretion (unchanged product + metabolites) during the same period was determined in percent of the administered dose level. Secnidazole is particularly different from tinidazole owing to its slower blood clearance. The apparent average half-life in the ten volunteers (5 men and 5 women) is about 17 hours for secnidazole and 13 hours for tinidazole. However, for both drugs, a difference between men and women was demonstrated: in female volunteers, the decrease in blood concentrations occurs a little quicker than in male volunteers. Regarding urinary excretion, it is also a little greater in female volunteers than in male volunteers.