Disposition and metabolism of the novel vasopressin antagonist, SK and E 101926, a synthetic octapeptide, in the isolated perfused rat liver (IPRL)

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5391966

Garvie, C T; Straub, K M; Landvatter, S W; Lynn, R K

SK and F 101926 is a potent competitive antagonist of vasopressin induced antidiuresis. In the rat >80% of the i.v. administered SK and F 101926 is excreted in bile in the form of metabolic products. The role of the liver in the metabolic degradation of SK and F 101926 was explored. Sprague Dawley rat livers were perfused (21 ml/min) in a single pass system. Radiolabeled SK and F 101926 (/sup 3/H-3, 3-D-TYR) was added to the perfusate at concentrations of 0.04, 0.4 and 4 ..mu..g/ml. Bile, liver and perfusate were analyzed by HPLC/LSC. The hepatic extraction ratio for SK and F 101926 was 0.076 +/- .013 at all concentrations studied. Liver and bile contained approximately half of the extracted radiolabel in the form of more than 15 metabolic products. The major (70%) biliary metabolite (ARG-COOH) at all doses studied was generated by enzymatic cleavage of the terminal amide bond. This metabolite was present in bile at concentrations 2000 times greater than in liver. These studies suggest that the liver contributes significantly to the extensive metabolic degradation of SK and F 101926 observed in vivo. The ARG-COOH, the major in vivo metabolite, was also the major metabolite in the IPRL.

• Research Organization: Smithkline Beckman, Philadelphia, PA
• OSTI ID: 5391966
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BILE
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CHROMATOGRAPHY
DIGESTIVE SYSTEM
GLANDS
HORMONES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MAMMALS
MATERIALS
METABOLISM
METABOLITES
ORGANS
PEPTIDE HORMONES
PERFUSED ORGANS
PITUITARY HORMONES
RATS
RODENTS
SEPARATION PROCESSES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASOPRESSIN
VERTEBRATES