PMID: 9531519May 16, 1998Paper

Intracellular and not intraluminal esterolysis of enalapril in kidney. Studies with the single pass perfused nonfiltering rat kidney

Drug Metabolism and Disposition : the Biological Fate of Chemicals
G L Sirianni, K S Pang

Abstract

Two possible sites of renal metabolism exist: intracellular, by enzymes within the peritubular cells, and intraluminal, by ecto-enzymes embedded on the brush border membrane. The esterolysis of enalapril to its dicarboxylate metabolite, enalaprilat, was studied in the isolated perfused, nonfiltering rat kidney preparation (NFK) and compared with that observed for the isolated perfused rat kidney (IPK) to ascertain the site of metabolic conversion. For the NFK, filtration was obliterated with the high oncotic pressure (8% bovine serum albumin in plasma) and ligation of the ureter, thus preventing enalapril from reaching intraluminal sites by filtration. The steady-state renal plasma clearance of enalapril in the NFK was 2.0 ml/min/g, a value similar to that (2.1 ml/min/g) observed previously for the IPK. The rate of appearance of enalaprilat, the metabolite, in venous plasma for the NFK (30 +/- 3% of the input rate of enalapril) was also comparable with that for the IPK (27 +/- 4%). Further, identification of the site of enalapril metabolism (cellular or luminal) was aided by simulations based on physiological models and parameters obtained previously on the renal handling of enalapril and enalaprilat. These parameters were opti...Continue Reading

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