Influence of hydrolysis products of aqua(1,1-bis(aminomethyl)cyclohexane)sulfatoplatinum(II) on toxicity in rats.
Aqueous solutions of the cisplatin analog aqua(1,1-bis(aminomethyl)-cyclohexane)sulfatoplatinum(II) (TNO-6, spiroplatin) principally contain hydrolyzed and oligomerized molecules. Sodium sulfate reduces the hydrolysis of the sulfato ligand. We investigated the influence of the equilibrium state on nephrotoxicity of spiroplatin in rats receiving 3 doses of 3 mg/kg with an interval of 8 days. Rats (n = 6) treated with spiroplatin solubilized in isoosmotic sodium sulfate (impaired hydrolysis) showed less toxicity as measured by proteinuria, platinum excretion and body weight, than the group treated with spiroplatin solubilized in 5% glucose. This result indicates that the presence of hydrolysis products plays a role in the toxicity of spiroplatin.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D003404:Creatinine / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000633:toxicity*; D010984:Platinum / Q000652:urine; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012996:Solutions
D009944:Organoplatinum Compounds; D012996:Solutions; D010984:Platinum; D003404:Creatinine; C040757:spiroplatin; D002945:Cisplatin