Renal handling of enalapril and enalaprilat: studies in the isolated red blood cell-perfused rat kidney
de Lannoy, I.A.; Nespeca, R.; Pang, K.S.
Journal of Pharmacology and Experimental Therapeutics 251(3): 1211-1222
1989
ISSN/ISBN: 0022-3565 PMID: 2557416 Document Number: 333294
An isolated recirculating or single pass red cell-perfused rat kidney preparation (IPK) was used to examine the differential handling of renal metabolites. In single pass experiments, enalapril was primarily metabolized to its polar, dicarboxylic acid metabolite, enalaprilat, and its fractional excretion (FE) was less than unity, suggesting net reabsorption. Its steady-state extraction ratio decreased from 0.3 to 0.2 at concentrations of 1.06 to 12.7 microM, due to a saturation of enzymes for esterolysis. Enalaprilat administered to the IPK was excreted into urine in a concentration-independent (0.41-35.3 microM) fashion, with FE values approximating unity, suggesting net filtration. Differences in handling were observed for enalaprilat, as a metabolite formed from enalapril and as an administered (preformed) species in the single pass IPK, when tracer concentrations of results in a greater metabolite clearance than that predicted from the administration of preformed metabolite.