Inactivation of cis-diamminedichloroplatinum (II) in blood by sodium thiosulfate

The mode of inactivation of cis-diamminedichloroplatinum (II) (DDP) in the bloodstream by sodium thiosulfate (STS) was investigated experimentally and clinically by a bioassay system using the phytohemagglutinin stimulation assay of human peripheral blood mononuclear cells. Active DDP in the plasma of dogs after 3 mg/kg of DDP injection, assessed by the bioassay system, was almost completely inactivated, when the level of STS in the plasma was more than 500 times higher at molar STS/DDP ratios than that of DDP. In 6 patients with hepatic malignancies who were treated with hepatic artery infusion of 3 mg/kg DDP and systemic STS, active DDP in the plasma was not detectable in the concurrent presence of STS at molar ratios of more than 500. Severe DDP toxicity in these patients was completely protected. The results indicate that an inactivation of DDP in the bloodstream after DDP injection and, further, an effective protection against DDP toxicity can be achieved by the concurrent presence of STS at molar ratios of more than 500 in the plasma of these patients.