PMID: 3746637Apr 1, 1986Paper

Renal transport kinetics of furosemide in the isolated perfused rat kidney

Journal of Pharmacokinetics and Biopharmaceutics
L J LeeD E Smith

Abstract

Direct quantitative data and corresponding theory are provided for the effect of protein binding on the renal transport of furosemide. Drug studies were performed with various combinations of bovine serum albumin and dextran. This resulted in a percent unbound (fu) of furosemide ranging from 0.785 to 85.8%. The corrected renal (CLr/GFR) and secretion (CLs/GFR) clearances of furosemide were observed to increase with percent free, but in a nonproportional manner. Plots of CLr/GFR or CLs/GFR vs. fu appeared to have a prominent y intercept as well as a convex ascending curve. In addition, the excretion ratio [ER = CLr/(fu . GFR)] was reduced from 60.8 to 8.72 as fu increased. Overall, the data were best fitted to a model in which two Michaelis-Menten terms were used to describe renal tubular transport, and secretion was dependent upon free drug concentrations in the perfusate. The results demonstrate that the renal mechanisms of furosemide excretion are more complex than previously reported and that active secretion may involve two different transport systems over the concentration range studied.

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Citations

Jan 1, 1993·European Journal of Clinical Pharmacology·P A SjöströmB G Odlind
Sep 10, 1998·Journal of Veterinary Pharmacology and Therapeutics·T M DykeK W Hinchcliff
Jun 1, 1996·The Journal of Pharmacy and Pharmacology·R MasereeuwF G Russel
Nov 1, 1991·Antimicrobial Agents and Chemotherapy·C A Rodriguez, D E Smith
Sep 7, 2006·Drug Development and Industrial Pharmacy·D R TaftI A Savant
Aug 1, 1989·British Journal of Clinical Pharmacology·A VianiG M Pacifici
Nov 12, 2003·The Journal of Pharmacology and Experimental Therapeutics·Habib HasannejadHitoshi Endou

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