Selective inhibition of the nephrotoxicity of cis-dichlorodiammineplatinum(II) by WR-2721 without altering its antitumor properties.
Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodiammineplatinum(II) (cisplatin) increased the resistance of Fischer 344 rats to cisplatin-induced nephrotoxicity  by a factor of 1.7, but did not alter the sensitivity of three different transplanted tumors to cisplatin-induced growth delay. As a consequence, it was possible to administer doses of cisplatin which would have been lethal in the absence of WR-2721 injection, resulting in a proportionally greater tumor response. WR-2721 can, therefore, increase the effectiveness of cisplatin therapy through selective protection against the toxic side effects of chemotherapy.
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006400:Hematocrit; D007668:Kidney / Q000187:drug effects*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D009946:Organothiophosphorus Compounds; D004999:Amifostine; D002945:Cisplatin