Absorption of oral enalapril in germ-free and microbially-associated rats.
The effect of microbial status and presence of food in the gastrointestinal (GI) tract on absorption of an orally administered antihypertensive drug [14C]-enalapril (1 mg/10 microCi/kg body weight) was studied in non-fasted and fasted germ-free (GF) and microbially-associated (MA) rats. The absorption was evaluated from blood samples taken 0.5, 2 and 4 h after the administration of enalapril. Drug levels in the lungs, liver, and duodenal mucosa were also measured by counting [14C]-radioactivities at 4 h after the drug administration. During the 4 h monitoring period enalapril was poorly absorbed in non-fasted rats as compared to fasted animals. In non-fasted rats, the absorption of enalapril was slightly slower in GF than in MA rats. In fasted rats, no difference was found between GF and MA animals. The results show that food in the GI tract substantially lowers or retards the absorption of enalapril in rats. The GF status of the GI tract, however, did not substantially affect the absorption of the ester-type drug enalapril.
Pelkonen
K
K
National Laboratory Animal Centre, University of Kuopio, Finland.
Ylitalo
P
P
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000097:blood; D004656:Enalapril / Q000493:pharmacokinetics*; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism; D005856:Germ-Free Life; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D051381:Rats
D004656:Enalapril; D002265:Carboxylic Ester Hydrolases; D007703:Peptidyl-Dipeptidase A