Absorption and disposition of LY127210, an orally effective hypotensive agent, in laboratory animals

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

OSTI ID:7034194

Turner, J C; White, J F; Sullivan, H R

The disposition, pharmacokinetics, and metabolic fate of LY127210, 7,8-dimethoxy-(1H)-3-benzazepin-2-amine hydrochloride, have been studied in mice, rats, dogs and monkeys. Pharmacokinetic and bioavailability studies in dogs and monkeys showed it to be well absorbed orally with maximum plasma levels of drug obtained within 4 hr. Following administration of /sup 14/C-LY127210, the plasma half-lives of parent and radiocarbon in rat were 11 hr and 45 hr (..beta..-phase), respectively. In dogs and monkeys parent half-lives were 11 hr (..beta..-phase) and 5.2 hr (monophasic) while half-lives of total radiocarbon were 145 hr (..beta..-phase) and 299 hr (..beta..-phase), respectively. Plasma concentrations of parent compound in rat, dog, and monkey following oral administration accounted for approximately 15% of circulating radiocarbon. Renal excretion was the major route of elimination. The major urinary species was LY127210; metabolic mechanisms included oxidative O-demethylation and deamination, aliphatic oxidation, and reduction. Radiocarbon tissue level studies in rat indicated wide distribution of drug and/or metabolites. Similar studies in monkeys indicated that the half-life of radiocarbon in tissues was equal to or greater than that in plasma and red blood cells. The long half-life of radiocarbon in blood was due to irreversible dose dependent binding of drug and/or metabolites to plasma albumin and to cellular hemoglobin.

• Research Organization: Eli Lilly and Co., Indianapolis, IN
• OSTI ID: 7034194
• 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
550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIHYPERTENSIVE AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
CARBON 14 COMPOUNDS
CARDIOVASCULAR AGENTS
CHEMOTHERAPY
CLEARANCE
DISTRIBUTION
DOGS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EXCRETION
HYPOTENSION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
MICE
MONKEYS
ORAL ADMINISTRATION
PRIMATES
RATS
REACTION KINETICS
RENAL CLEARANCE
RODENTS
THERAPY
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES