Effect of probenecid and N'-methylnicotinamide on renal handling of cis-dichlorodiammineplatinum-II in rats

Abstract

The renal handling of cisplatin was investigated in Sprague-Dawley rats in the presence and absence of probenecid and N'-methylnicotinamide. The renal clearance of free cisplatin was not significantly different from the glomerular filtration rate. N'-Methylnicotinamide, an organic cation, did not affect cisplatin clearance. Administration of probenecid, an organic anion, resulted in a significant increase in cisplatin clearance to 169% of the glomerular filtration rate. These results suggest that cisplatin or a metabolite is excreted by the kidney by a complex process which includes glomerular filtration, secretion and active reabsorption via the organic acid transport system.