Effect of probenecid and N'-methylnicotinamide on renal handling of cis-dichlorodiammineplatinum-II in rats.
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.
D000818:Animals; D002945:Cisplatin / Q000378:metabolism*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009536:Niacinamide; D011339:Probenecid; D002945:Cisplatin; C008472:N-methylnicotinamide