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  • Title: Disposition and metabolism of the angiotensin-converting enzyme inhibitor [4S-[4 alpha, 7 alpha, (R*), 12b beta]]-7-[S-(1-ethoxycarbonyl-3- phenylpropyl)amino]-1,2,3,4,6,7,8,12b-octahydro-6-oxo- pyrido[2,1-a][2]benzazepine-4-carboxylic acid in monkeys and dogs.
    Author: Cheng H, Stuhler JD, Dorrbecker BR, Gordon WP.
    Journal: Drug Metab Dispos; 1991; 19(1):212-7. PubMed ID: 1673401.
    Abstract:
    [4S-[4 alpha, 7 alpha, (R*),12b beta]]-7-[S- (1-ethoxycarbonyl-3-phenylpropyl)amino]-1,2,3,4,6,7,8, 12b-octahydro-6-oxo-pyrido[2,1-a][2]benzazepine-4-carboxylic acid (MDL 27,210) is the ethyl ester prodrug of a potent angiotensin-converting enzyme inhibitor, MDL 27,088. After a single dose of [14C]MDL 27,210 (3 mg/kg iv), MDL 27,210 was rapidly eliminated from the plasma of monkeys and dogs with a terminal half-life of approximately 0.3 hr. The steady-state volume of distribution was 0.15 liter/kg in dogs and 0.28 liter/kg in monkeys. Monkeys excreted 52% of the 14C dose in the feces and 41% in the urine; dogs excreted 80% of the 14C dose in the feces and 14% in the urine. The presence of a large fraction of the 14C dose in the feces of both species following iv administration suggests that significant biliary excretion occurred. MDL 27,210 administered iv to monkeys and dogs was rapidly and extensively (greater than 99.9%) metabolized, primarily to its diacid metabolite, MDL 27,088. The half-life of MDL 27,088 was 2.2 hr in dogs and 3.6 hr in monkeys.
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