Physiological disposition and metabolism of enalapril maleate in laboratory animals

Journal Article · · Drug Metab. Dispos.; (United States)

OSTI ID:6657275

Tocco, D J; deLuna, F A; Duncan, A E; Vassil, T C; Ulm, E H

N-(1-(S)-carboxy-3-phenylpropyl)-L-alanyl-L-proline (MK-422), is a potent angiotensin I-converting enzyme (ACE) inhibitor, but as a diacid is poorly absorbed in laboratory animals. Enalapril maleate, the monoethyl ester of MK-422, proved to be significantly better absorbed in both rats and dogs. Peak levels of radioactivity in plasma occurred in 30 min in rats and 2 hr in dogs after a single dose of /sup 14/C-enalapril maleate (1 mg/kg, po). Rats excreted 26% of the dose in the urine and 72% in the feces in 72 hr; dogs excreted 40% of the dose in the urine and 36% in the feces. After the intravenous dose, the presence of radioactivity in the feces of both species suggested that some biliary excretion had occurred. Absorption was estimated to be 34% in the rat and 61% in the dog. The major metabolite of enalapril maleate in dogs, accounting for 86% of the urine radioactivity, was identified as MK-422 by GC/MS. A procedure was developed for the quantitation of MK-422 and enalapril in plasma and urine by their inhibition of purified ACE. The assays showed that enalapril was absorbed intact in dogs and converted to MK-422 after absorption.

• Research Organization: Merck Institute for Therapeutic Research, West Point, PA
• OSTI ID: 6657275
• Journal Information: Drug Metab. Dispos.; (United States), Vol. 10:1
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARBON 14 COMPOUNDS
ISOTOPE APPLICATIONS
CARBOXYLIC ACID ESTERS
METABOLISM
ABSORPTION
BIOLOGICAL PATHWAYS
DOGS
EXCRETION
FECES
METABOLITES
RATS
URINE
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CLEARANCE
ESTERS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
RODENTS
VERTEBRATES
WASTES
550201* - Biochemistry- Tracer Techniques