Metabolism and excretion of centbutindole (neuroleptic) in rats after oral administration

The metabolism and excretion of centbutindole was studied in Sprague-Dawley rats after oral administration. The percentage of dose excreted was monitored over 4 days. Efforts were also directed towards evaluating the stability of centbutindole in various in-vitro biomatrices. Centbutindole was found to be metabolised in rats and only a negligible amount of parent drug was excreted. The percentage of the dose excreted in bile and faeces was 0.2% and 0.6%, respectively. No drug was found in urine after oral administration, but after an intravenous dose only 0.0012% of the dose was eliminated through urine. Two metabolites, dealkylated metabolite and hydroxy metabolite, were identified by ion spray LC/MS/MS, using a combination of parent ion and product ion scanning techniques. The major routes of metabolism of centbutindole include reduction of the carbonyl functional group in the butyrophenone side chain and N-dealkylation of the butyrophenone side chain attached to the pyrazinopyridoindole ring nitrogen at position 2. The hydroxy metabolite was excreted negligibly in bile, although it was present in the form of glucuronide conjugates more in comparison to its free form.