Renal clearance of carprofen in the isolated perfused rat kidney

Abstract

The renal clearance of the anti-inflammatory agent, carprofen, was studied in the isolated perfused rat kidney (IPK). The dosing range used (0.5-25 mg) produced perfusate concentrations comparable to and greater than therapeutic plasma concentrations expected in man. In vitro studies in the rat were done as a basis for comparison to the in vitro IPK parameters. Because of its extensive binding (greater than 99%) to the protein fraction of the perfusate, the urinary excretion of carprofen was low an perfusate concentration-dependent. The calculation of the tubular transit rate at each carprofen concentration indicated the following net mechanism(s) of renal carprofen clearance: filtration at low concentration, reabsorption at intermediate concentrations, and secretion at the highest concentration. At low urinary pH and flow rates, reabsorption effectively counteracted secretion. The present in vitro studies suggest that carprofen is excreted by the kidney by the pathway common to a variety of organic acids.