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.