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Abstract

Selectivity of the cimetidine-induced alterations in the renal handling of organic substrates in humans. Studies with anionic, cationic and zwitterionic drugs.

J van Crugten, F Bochner, J Keal and A Somogyi
Journal of Pharmacology and Experimental Therapeutics February 1986, 236 (2) 481-487;
J van Crugten
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F Bochner
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J Keal
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A Somogyi
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Abstract

Cimetidine reduces the renal clearances of the organic cations procainamide and n-acetylprocainamide in humans and in vitro preparations by inhibition of renal cationic proximal tubular secretion. The aim of this study was to investigate in humans the selectivity of cimetidine in altering the renal handling of three different organic ions as drug substances: anion (cephalothin), cation (ranitidine) and zwitterion (cephalexin). The study was conducted in six healthy subjects who received the above drugs as single doses with and without chronic cimetidine administration. Cimetidine had no statistically significant (P greater than .05) effect on cephalothin disposition including renal clearance, but significantly reduced the renal clearance of ranitidine by over 40% between 4 and 12 hr after administration, with a concomitant increase in ranitidine plasma concentrations and elimination half-life prolongation. In addition, the renal clearance of cephalexin was reduced by cimetidine by 27% between 1 and 2 hr, but there was no change in cephalexin plasma concentrations and elimination half-life. These findings confirmed the hypothesis that cimetidine-mediated inhibition of renal drug clearance in humans is selective for a common cationic secretory transport mechanism in the proximal tubule of the kidney, rather than a nonspecific action on renal function.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 236, Issue 2
1 Feb 1986
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Abstract

Selectivity of the cimetidine-induced alterations in the renal handling of organic substrates in humans. Studies with anionic, cationic and zwitterionic drugs.

J van Crugten, F Bochner, J Keal and A Somogyi
Journal of Pharmacology and Experimental Therapeutics February 1, 1986, 236 (2) 481-487;

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Abstract

Selectivity of the cimetidine-induced alterations in the renal handling of organic substrates in humans. Studies with anionic, cationic and zwitterionic drugs.

J van Crugten, F Bochner, J Keal and A Somogyi
Journal of Pharmacology and Experimental Therapeutics February 1, 1986, 236 (2) 481-487;
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