Studies on the biotransformation of indoramin in the patas monkey

Abstract

1. Studies on absorption, excretion and biotransformation of the antihypertensive agent indoramin (3-[2-(4-benzamidopiperidino)ethyl]indole hydrochloride) have been carried out in patas monkeys.

2. Absorption of the drug was extensive, as indicated by <8% of the dose appearing in faeces as the unchanged compound.

3. Approx. 35% of an orally administered dose of the ³H-labelled drug was recovered in urine while a similar amount was found in faeces. Urinary excretion of total ³H was mono-exponential with a half-life of 17 h.

4. Biotransformation was extensive, the unchanged drug constituting <4.5% of the urinary metabolites. The principal identified metabolites were a sulphate conjugate of 3-[2-(4-benzamidopiperidine)ethyl]indol-6-ol and an acid-labile conjugate of the parent drug. A minor metabolite resulting from N-dealkylation of the drug was identified as 4-benzamidopiperidine. Small amounts of 3-[2-(4-[4-hydroxybenzamido]piperidino)-ethyl]indole were found in a dichloromethane extract of acid-hydrolysed urine.

5. The faeces contained only negligible amounts of conjugated metabolites. The principal components were the indole-6-hydroxylated derivative of the parent drug with smaller amounts of the 5-hydroxylated compound and the unchanged compound.