Kinetics of sodium thiosulfate, a cisplatin neutralizer

Clin Pharmacol Ther. 1984 Mar;35(3):419-25. doi: 10.1038/clpt.1984.53.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Chromatography, High Pressure Liquid
  • Cisplatin / antagonists & inhibitors*
  • Cisplatin / therapeutic use
  • Female
  • Humans
  • Infusions, Parenteral
  • Kinetics
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Thiosulfates / metabolism
  • Thiosulfates / pharmacology*

Substances

  • Thiosulfates
  • sodium thiosulfate
  • Cisplatin