title: Physiological disposition of CGS 16617 in rat, dog, and man.
abstract: The disposition and metabolism of CGS 16617 (3-[(5-amino-1-carboxy-1S-pentyl)amino],2,3,4,5-tetrahydro-2-oxo-3S-1H-1 - benzazepine-1-acetic acid), and angiotensin l-converting enzyme inhibitor, were investigated in rats, dogs, and man. In rats, a single oral dose of 10 mg/kg 14C-CGS 16617 afforded peak plasma concentrations of drug between 0.5 and 6 hr of dosing. The AUC was on average 9.6% of that after iv administration of the same dose, indicating low oral absorption of the drug. The apparent volumes of distribution, V1 and Vdss, were 0.45 and 2.5 liters/kg, respectively. Disappearance of the drug from plasma after the iv dose was biphasic, with mean half-lives of 0.5 and 13 hr, respectively, for the lambda 1 and lambda 2 phases. After single iv doses (10 mg/kg) to dogs and rats, 14CGS 16617 was almost exclusively eliminated by the renal route, with urinary recoveries of greater than 90% of dose. The same dose administered orally gave urinary recoveries of less than 10% of the dose in rats and about 15% in the dog. The remainder of the dose was eliminated in the feces. Bile duct-cannulated rats excreted less than 3% of an oral 10 mg/kg dose in the bile, in 24 hr. In man (N = 4), a single oral dose of 100 mg 14C-CGS 16617 resulted in peak plasma concentrations of 0.02-0.07 microgram of drug eq/ml between 4 and 6 hr of dosing. The mean terminal half-life was estimated at 81 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Research Department, CIBA-GEIGY Corporation, Ardsley, NY 10502.
authors.forename: H
authors.initials: H
authors.lastname: Egger
authors.forename: G
authors.initials: G
authors.lastname: Kochak
authors.forename: P
authors.initials: P
authors.lastname: Robertson
authors.forename: R
authors.initials: R
authors.lastname: Iannucci
authors.forename: F A
authors.initials: FA
authors.lastname: Rufino
authors.forename: F
authors.initials: F
authors.lastname: Stancato
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001552:Benzazepines / Q000493:pharmacokinetics*; D002855:Chromatography, Thin Layer; D004285:Dogs; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D001552:Benzazepines; C052134:libenzapril