Thiosulfate Pharmacokinetics in Normal and Anuric Dogs

Abstract

Abstract

Cyanide (CN) toxicity has recently become increasingly a clinical problem with the greater use of Laetrile for cancer treatment and of sodium nitroprusside for blood pressure control. Sodium thiosulfate is an excellent antidote for CN toxicity but not all aspects of its pharmacokinetics have been adequately studied. Applying a specific thiosulfate assay, we measured endogenous thiosulfate, the response to CN infusion, and disappearance after iv injection in normal and anuric dogs. Endogenous plasma concentration was approximately 1 mg/dl; the bile concentration was 15 times higher but biliary excretion accounted for less than 2%, compared to renal excretion. Cyanide infusion decreased endogenous plasma thiosulfate 33% before death. The fast component of the thiosulfate disappearance curve was similar, 3 min, after iv injection (150 mg/kg), while the second component was markedly prolonged in anuric dogs (239 min) compared to controls (47 min). Therefore, a constant infusion of thiosulfate would appear to be the best method of maintaining the high plasma concentration necessary for CN detoxification during the continuous administration or absorption of CN-producing compounds.