REDUCTIVE METABOLISM AND ITS ROLE IN THE DISPOSITION OF THE HYDROXAMIC ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR IDRAPRIL CALCIUM IN RAT

1. The metabolism of C-14-idrapril calcium, the prototype of a new cla ss of angiotensin converting enzyme inhibitors, was studied in rat aft er a single intravenous administration. Plasma, urine, faeces, and bil e were assayed for total and hplc-fractionated radioactivity. 2. Only one major metabolite (M1, -sarcosinamide-cis-1,2-cyclohexanedicarboxyl amide) 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 bein g the most abundant product. In bile, two metabolites (M1, M3), but no t the parent compound, were found. 3. In conclusion intravenous idrapr il undergoes hepatic reduction to M1 and hydrolysis to M2. M1 can be g lucuronated to M3 and both are partially excreted in the bile and furt her processed in the gut to reabsorbable radioactive species.