Reductive metabolism and its role in the disposition of the hydroxamic angiotensin-converting enzyme inhibitor idrapril calcium in rat

1. The metabolism of 14C-idrapril calcium, the prototype of a new class of angiotensin-converting enzyme inhibitors, was studied in rat after a single intravenous administration. Plasma, urine, faeces, and bile were assayed for total and hplc-fractionated radioactivity. 2. Only one major metabolite (M1, 2-sarcosinamide-cis-1,2-cyclohexanedicarboxylamide) was observed, along with idrapril, in plasma. Three metabolites (M1, M2, cis-1,2-cyclohexanedicarboxylic acid, and M3, a glucuronate derivative of M1) were present in 0-8-h urine, unchanged idrapril being the most abundant product. In bile, two metabolites (M1, M3), but not the parent compound, were found. 3. In conclusion intravenous idrapril undergoes hepatic reduction to M1 and hydrolysis to M2. M1 can be glucuronated to M3 and both are partially excreted in the bile and further processed in the gut to reabsorbable radioactive species.