Metabolic disposition of CI-924, a new lipid regulating agent, in laboratory animals

Conference · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:7034142

Mertz, N; Windsor, B; Chang, T

The disposition of carbon-14 labeled CI-924 (I), 5,5'-(1,1-biphenyl)-2,5 diyl-bis(oxy)-bis-2,2'-dimethylpentanoic acid, was studied in beagle dogs and rats following single 10 mg/kg po doses. Serial plasma, urine and fecal samples were collected up to 168 hr and analyzed for total radioactivity. Peak /sup 14/C plasma concentrations of 31 mcg/ml (dogs) and 66 mcg/ml (rats) were attained within 0.5 and 1.0 hr after dosing. The concentrations declined thereafter with estimated half life of 11 and 5 hr in rats and dogs, respectively. TLC radiochromatography revealed that I was the only component in circulating blood. Tissue distribution study in rats showed that the highest /sup 14/C concentrations were found in plasma and liver with decreasing concentrations in lung, heart, kidney, skin, gonads, spleen, fat, muscle, adrenals, and brain. All tissue concentrations declined in parallel with plasma levels with half lives of 14-22 hr. Urinary and fecal excretion accounted for 1-3% and 92-96% of the dose, respectively. Balance study in bile duct cannulated rats showed that 90%, 1%, and 1% of the dose was excreted in bile, urine, and feces. Unchanged drug and varying amounts of its conjugate were the only products present in bile, urine or feces. These results indicate that I was completely absorbed and eliminated primarily by biliary excretion in the form of unchanged drug and its conjugate.

• Research Organization: Warner-Lambert Research Div., Ann Arbor, MI
• OSTI ID: 7034142
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BEAGLES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD
BLOOD PLASMA
BODY FLUIDS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHROMATOGRAPHY
CLEARANCE
DISTRIBUTION
DOGS
EXCRETION
FECES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METABOLISM
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
RATS
RODENTS
SEPARATION PROCESSES
TISSUE DISTRIBUTION
TRACER TECHNIQUES
URINE
VALERIC ACID
VERTEBRATES
WASTES