Abstract

The renal handling of sulfisoxazole was evaluated in man and dog with clearance studies and stop-flow analysis. Excretion is altered by urine pH in both species and by urine flow changes in the dog. In dog renal clearance studies, no correlation could be made between the increased filtered load of sulfonamide and its clearance values. Probenecid and dinitrophenol significantly decreased the excretion of sulfisoxazole under conditions of urinary alkalinization. The data from the present clearance studies in man and dog suggest two mechanisms for the renal handling of sulfonamide: passive reabsorption-secretion and active secretion. To test the latter mechanism, stop-flow protocol was utilized in anesthetized dogs. Data from these studies indicate an active secretory transport component in the proximal renal tubule. Furthermore, inhibition of proximal tubular secretion was obtained in the presence of probenecid. On the other hand, tubular reaborption of sulfisoxazole as a passive component was altered by urinary alkalinization but was unaffected by probenecid administration. Therefore, it appears that several mechanisms, i.e., active secretion and passive reabsorption-secretion, are involved in the renal handling of sulfisoxazole under certain laboratory conditions in both man and dogs.