Comparative study on the disposition of a new orally active dopamine prodrug, N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine (TA-870) and dopamine hydrochloride in rats and dogs

Journal Article · Thu Sep 01 04:00:00 EDT 1988 · Drug Metab. Dispos.; (United States)

OSTI ID:6326625

Yoshikawa, M; Endo, H; Otsuka, M; Yamaguchi, I; Harigaya, S

The pharmacokinetics of a dopamine derivative, TA-870, and dopamine (DA) after oral administration are compared in rats and dogs. The maximum concentrations of free DA in plasma after oral administration of TA-870 were 150 ng/ml in the rat (30 mg/kg) and 234 ng/ml in the dog (33.5 mg/kg). On the contrary, the maximum plasma concentrations after oral administration of DA at an equimolar dose to TA-870 were 12 ng/ml in the rat (12 mg/kg) and 36 ng/ml in the dog (13.5 mg/kg). The AUC values of free DA in plasma after oral administration of TA-870 (30 or 33.5 mg/kg) were 4-6 times higher than those after DA in both animal species. The peak tissue levels of radioactivity in rats after oral administration of (/sup 14/C)TA-870 (30 mg/kg) were also 5.5 times higher in the liver and 1-2 times higher in other tissues than those after (/sup 14/C)DA dose (12 mg/kg). In rats, the main excretion route of radioactivity after oral administration of (/sup 14/C)TA-870 or DA was via the urine. The total recoveries of radioactivity in the urine and feces were 91-96% of the dose within 24 hr for both compounds. Biliary excretion in rats accounted for 19.8% of the dose of (/sup 14/C)TA-870 and 12.6% of the dose of (/sup 14/C)DA within 24 hr. These results demonstrate that TA-870 was well absorbed from the digestive tract, extensively metabolized to dopamine, and proved to be an orally usable dopamine prodrug.

• Research Organization: Tanabe Seiyaku Co., Ltd., Saitama (Japan)
• OSTI ID: 6326625
• Journal Information: Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 16:5; ISSN DMDSA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BILE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BIOLOGICAL VARIABILITY
BODY FLUIDS
CARBON 14 COMPOUNDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
COMPARATIVE EVALUATIONS
DISTRIBUTION
DOGS
DOPAMINE
DRUGS
GENETIC VARIABILITY
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METABOLISM
NEUROREGULATORS
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
RATS
REACTION KINETICS
RODENTS
SYMPATHOMIMETICS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES