Renal transport kinetics of furosemide in the isolated perfused rat kidney

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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 ofCLr/GFR orCLs/GFR vs.fu appeared to have a prominenty 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 asfu increased. Overall, the data were best fitted to a model in which two Michaelis-Menten terms wre 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.