Comparative nephrotoxicity of tetraplatin and cisplatin in rats.
Cisplatin, a useful therapeutic agent against many forms of cancer, possesses significant nephrotoxicity, necessitating a search for agents with similar therapeutic profiles but with less potential for renal damage. Since tetraplatin, another platinum analog being evaluated in phase I clinical trials, has a favorable therapeutic profile when compared to cisplatin, we examined the comparative nephrotoxicity of tetraplatin and cisplatin in rats when both compounds were administered at equimolar doses. Based on various parameters, we found that tetraplatin was less nephrotoxic. In vivo injections of equimolar doses of tetraplatin caused a much lesser rise in serum urea nitrogen and creatinine when compared to cisplatin. In vitro, renal slice accumulation of 3H-p-aminohippurate and 14C-tetraethylammonium was significantly decreased after cisplatin but not after tetraplatin. Morphological damage in the kidneys was more severe after cisplatin compared to tetraplatin. We conclude through in vivo and in vitro methodology that tetraplatin is significantly less nephrotoxic than cisplatin at comparable therapeutic doses.
Rahman
A
A
Department of Medicine, Georgetown University Hospital, Washington, DC.
Roh
J K
JK
Preuss
H G
HG
D000818:Animals; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007928:Lethal Dose 50; D008297:Male; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000493:pharmacokinetics; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D009944:Organoplatinum Compounds; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D003404:Creatinine; D002945:Cisplatin; C049777:ormaplatin; D010130:p-Aminohippuric Acid