Disposition of /sup 14/C-LY195115 (1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl-6-/sup 14/C)-2H-indol-2-one), a potent cardiotonic drug, in several animal species

Conference · Tue Mar 04 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6797511

Bernstein, J R; Miller, B J; Franklin, R B

Following the oral administration of /sup 14/C-LY195115 to rats, mice, dogs, and monkeys (25,15,5, and 5 mg/kg, respectively), between 40 and 60% of the radioactivity was excreted into the urine within 24 hr. The elimination half-time of radioactivity from plasma was approximately 5 hr for rats and mice, 8 hr for monkeys, and 14 hr in dogs. Analysis of the 24 hr urine by thin-layer chromatography (tlc) revealed that the predominant radioactive moiety from all species was parent drug (> 30% of the dose). The urinary metabolite profile in the monkey showed parent drug and 2 polar, minor metabolites. The pattern was similar in rats, mice and dogs. Additionally in monkeys there was a very polar metabolite which was not conjugated with ..beta..-glucuronic acid. The major metabolite in the urine was isolated and shown to have a molecular weight of 255 (LY195115=257). Synthesis of the dehydro derivative of LY195115 indicated that the metabolite was identical to this material. A tissue distribution study in rats, following an oral dose of /sup 14/C-LY195115 resulted in no apparent accumulation of radioactivity in any particular organ.

• Research Organization: Eli Lilly and Co., Indianapolis, IN
• OSTI ID: 6797511
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIHYPERTENSIVE AGENTS
BIOLOGICAL HALF-LIFE
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD
BLOOD PLASMA
BODY FLUIDS
CARBON 14 COMPOUNDS
CARDIOVASCULAR AGENTS
CARDIOVASCULAR DISEASES
CHEMOTHERAPY
CHROMATOGRAPHY
CLEARANCE
DISEASES
DISTRIBUTION
DOGS
DRUGS
EXCRETION
HYPERTENSION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METABOLISM
METABOLITES
MICE
MONKEYS
ORAL ADMINISTRATION
PRIMATES
RATS
RODENTS
SEPARATION PROCESSES
SYMPTOMS
THERAPY
THIN-LAYER CHROMATOGRAPHY
TISSUE DISTRIBUTION
TRACER TECHNIQUES
URINE
VASCULAR DISEASES
VERTEBRATES
WASTES