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Abstract

Differential renal handling of angiotensin-converting enzyme inhibitors enalaprilat and lisinopril in rats.

J H Lin, I W Chen, E H Ulm and D E Duggan
Drug Metabolism and Disposition May 1988, 16 (3) 392-396;
J H Lin
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I W Chen
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E H Ulm
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D E Duggan
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Abstract

Enalaprilat, the active metabolite of enalapril, and its lysine analogue lisinopril are potent nonsulfhydryl angiotensin-converting enzyme inhibitors. Earlier studies from our laboratories demonstrated that neither drug is significantly metabolized, and both are almost exclusively eliminated by renal excretion. This report compares the renal excretory mechanisms for these structurally related compounds in the rat. After an iv, 1-mg/kg dose, ratios of renal clearance (CLR) of unbound drug to glomerular filtration rate (GFR) for enalaprilat and lisinopril were 2.72 +/- 0.70 and 1.01 +/- 0.18, respectively, suggesting that enalaprilat, but not lisinopril, was actively secreted by the kidneys. Treatment with probenecid and p-aminohippuric acid, potent competitive inhibitors for the renal anionic transport system, caused a profound decrease in the renal clearance of enalaprilat to the level of GFR. The CLR/fu.GFR, where fu is the unbound fraction, became 1.10 +/- 0.09 and 1.25 +/- 0.25, respectively. These results and the fact that quinine, a potent inhibitor for the cationic transport system, had little effect on the renal clearance of enalaprilat indicated that enalaprilat is secreted by the organic anion transport system. On the other hand, probenecid, p-aminohippuric acid, and quinine had no effect on the renal clearance of lisinopril, suggesting that lisinopril is eliminated exclusively by glomerular filtration.

 

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Drug Metabolism and Disposition
Vol. 16, Issue 3
1 May 1988
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Abstract

Differential renal handling of angiotensin-converting enzyme inhibitors enalaprilat and lisinopril in rats.

J H Lin, I W Chen, E H Ulm and D E Duggan
Drug Metabolism and Disposition May 1, 1988, 16 (3) 392-396;

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Abstract

Differential renal handling of angiotensin-converting enzyme inhibitors enalaprilat and lisinopril in rats.

J H Lin, I W Chen, E H Ulm and D E Duggan
Drug Metabolism and Disposition May 1, 1988, 16 (3) 392-396;
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