Renal handling of cisplatin: interactions with organic anions and cations in the dog.
Cis-diamminedichloroplatinum (II) (cisplatin CDDP) is an extremely potent chemotherapeutic agent. Its efficacy, however, is hindered by the cumulative dose-dependent nephrotoxicity which can lead to permanent renal impairment. The mechanisms of the renal transport of cisplatin are not clear. As a first step towards understanding the renal handling of cisplatin we studied its renal clearance in dogs, as well as the effects of organic anion and cation administration on cisplatin. Our results document net tubular secretion of cisplatin. Both an organic anion (probenecid) and cations (quinidine, cimetidine, ranitidine) significantly decreased renal clearance of free CDDP without affecting GFR.
Klein
J
J
Department of Pediatrics and Research Institute, Hospital for Sick Children, Toronto, Ontario.
Bentur
Y
Y
Cheung
D
D
Moselhy
G
G
Koren
G
G
D000818:Animals; D000838:Anions / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism; D002412:Cations / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D002945:Cisplatin / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008657:Metabolic Clearance Rate; D011339:Probenecid / Q000494:pharmacology; D011485:Protein Binding; D011802:Quinidine / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology
D000838:Anions; D001798:Blood Proteins; D002412:Cations; D002927:Cimetidine; D011899:Ranitidine; D011802:Quinidine; D011339:Probenecid; D002945:Cisplatin