Inactivation of cis-diamminedichloroplatinum (II) in blood and protection of its toxicity by sodium thiosulfate in rabbits.
The mode of inactivation of cis-diamminedichloroplatinum(II) (DDP) in the bloodstream and protection from its toxicity by sodium thiosulfate (STS) were investigated in rabbits. Plasma ultrafiltrate in rabbits given 5 mg/kg DDP IV and various excess molar ratios of STS IV were assayed for the active platinum levels with a new microbiological assay system using an E. coli strain. The active platinum species in the plasma were inactivated completely by co-administration of a 400-fold excess of STS IV. The rabbits were almost completely protected against both BUN increase and body weight loss normally caused by DDP when 400-fold doses of STS were given. Diuretic effects were also observed. Our data provide evidence for the basis of optimum use of STS to protect against DDP toxicity.
D000818:Animals; D002945:Cisplatin / Q000097:blood* / Q000494:pharmacology / Q000633:toxicity; D004347:Drug Interactions; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D007700:Kinetics; D011817:Rabbits; D013054:Spectrophotometry, Atomic; D013885:Thiosulfates / Q000494:pharmacology*; D014462:Ultrafiltration
D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin