RENAL HANDLING OF TOBRAMYCIN IN THE ISOLATED-PERFUSED RAT-KIDNEY

The renal handling of tobramycin (TOB), an aminoglycoside antibiotic ( AG), was studied using a single-pass isolated perfused rat kidney with moment analysis. In the bolus administration study at tracer concentr ation (7.4 mu M), 32% Of the glomerular-filtrated TOB remained in the lumen, but no TOB was found in the vein. This ratio of the luminal upt ake was reduced in a dose-dependent manner. Other aminoglycosides such as gentamicin inhibited this uptake, but tetraethylammonium and gluco samine had no effect. In addition, under the alkalinuria condition, TO B uptake was decreased to 67% of the control value. This indicated tha t TOB has mainly been taken into the renal epithelial cells from their luminal site and that this uptake process was saturable and specific for AGs which have more than one cationic group. The present findings should be helpful in developing a method to reduce the nephrotoxicity of AGs and to identify their toxicity mechanisms.