Pharmacokinetics and toxicity of tolonium chloride in sheep.
The pharmacokinetic disposition, urinary excretion and toxicity of tolonium chloride were determined after i.v. administration to sheep. Pretreatment with sodium nitrite significantly decreased the volume of the central compartment, apparent volume of distribution, area under the concentration-time curve, and total body clearance of tolonium chloride. Urinary excretion of tolonium chloride and its metabolite, leucotolonium chloride, together accounted for less than 15% of the administered dose in sheep receiving sodium nitrite and less than 10% of the administered dose in control sheep. The LD50 of tolonium chloride was 10 mg/kg with a 95% confidence interval of 7.35-13.60 mg/kg. Comparison with previously published data describing the pharmacokinetics and toxicity of a related compound, methylene blue, indicated that tolonium chloride has a higher volume of distribution and a narrower therapeutic index.
Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078, USA.
L A
LA
Cudd
G E
GE
Burrows
C R
CR
Clarke
D000818:Animals; D001774:Blood Chemical Analysis; D004396:Coloring Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D010084:Oxidation-Reduction; D012044:Regression Analysis; D012756:Sheep / Q000097:blood*; D014048:Tolonium Chloride / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D014556:Urine / Q000737:chemistry
D004396:Coloring Agents; D014048:Tolonium Chloride