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Renal tubular secretion of amiloride and its inhibition by cimetidine in humans and in an animal model.

Author(s): Somogyi AA, Hovens CM, Muirhead MR, Bochner F

Affiliation(s): Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.

Publication date & source: 1989-03, Drug Metab Dispos., 17(2):190-6.

Publication type: Clinical Trial; Randomized Controlled Trial

The histamine H2 antagonist cimetidine has been shown to reduce the renal tubular secretion of other organic cations through competition for the specific transport system with organic cations in the renal proximal tubule. The potential interaction between cimetidine and the potassium-sparing diuretic amiloride was investigated in humans and in the isolated perfused rat kidney. A chronic dosing study was conducted in eight healthy subjects who received, in random order, amiloride (5 mg daily), cimetidine (400 mg twice daily), both drugs together, and a control phase in which no drug was present. Cimetidine reduced the renal clearance of amiloride by a mean of 17%, from 358 +/- 134 to 299 +/- 118 ml/min (p less than 0.05), and the urinary excretion of amiloride from 65 +/- 11 to 53 +/- 13% of the dose (p less than 0.05). Amiloride reduced the excretion of cimetidine from 43 +/- 7 to 32 +/- 9% of the dose (p less than 0.05) and the area under the plasma concentration-time curve for cimetidine by a mean of 14% (p less than 0.05) but had no effect on the renal clearance of cimetidine. In the perfused rat kidney, cimetidine reduced the amiloride unbound renal clearance to glomerular filtration rate ratio from 5-7:1 to 1-2:1 (p less than 0.05). These studies demonstrate that cimetidine inhibits the renal tubular secretion of amiloride in humans and in rats to a similar extent. In addition, in humans the gastrointestinal absorption of both amiloride and cimetidine appear to be reduced by each other, by an as yet unknown mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

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