PHARMACOKINETICS AND TOXICITY OF TOLONIUM CHLORIDE IN SHEEP

The pharmacokinetic disposition, urinary excretion and toxicity of tol onium chloride were determined after iv administration to sheep. Pretr eatment with sodium nitrite significantly decreased the volume of the central compartment, apparent volume of distribution, area under the c oncentration-time curve, and total body clearance of tolonium chloride . Urinary excretion of tolonium chloride and its metabolite, leuco-tol onium chloride, together accounted for less than 15% of the administer ed dose in sheep receiving sodium nitrite and less than 10% of the adm inistered dose in control sheep. The LD(50) of tolonium chloride was 1 0 mg/kg with a 95% confidence interval of 7.35-13.60 mg/kg. Comparison with previously published data describing the pharmacokinetics and to xicity of a related compound, methylene blue, indicated that tolonium chloride has a higher volume of distribution and a narrower therapeuti c index.