Kinetics of sodium thiosulfate, a cisplatin neutralizer

Sodium thiosulfate kinetics were studied in eight subjects, six of whom were given the drug as a cisplatin neutralizer. Thiosulfate at a dose of 12 gm/m2 was injected by continuous intravenous infusion over 6 hr. Under these conditions, steady-state plasma concentrations were not achieved and apparent volume of distribution could not be calculated. The drug was eliminated from plasma by first-order kinetics, and the data best fit a one-compartment kinetic model with a t1/2 (mean +/- SD) of 80 +/- 38 min. Total body thiosulfate clearance was 190 +/- 76 ml/min/m2 and renal clearance was 50 +/- 11 ml/min/m2. The plasma elimination t1/2 and renal thiosulfate clearance correlated poorly with clearance of endogenous creatinine. Only 28.5% +/- 9.4% of the thiosulfate was recovered unchanged in the urine. Urinary excretion was rapid, with approximately 95% of recoverable drug eliminated within 4 hr after termination of the infusion. No toxic effects of thiosulfate were observed. These data provide the basis for the rational development of dose schedules when sodium thiosulfate is used as a cisplatin neutralizer.