Physiological disposition and metabolism of enalapril maleate in laboratory animals
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), Journal Name: Drug Metab. Dispos.; (United States) Vol. 10:1; ISSN DMDSA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ABSORPTION
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CARBOXYLIC ACID ESTERS
CLEARANCE
DOGS
ESTERS
EXCRETION
FECES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METABOLISM
METABOLITES
ORGANIC COMPOUNDS
RATS
RODENTS
URINE
VERTEBRATES
WASTES