Pharmacokinetics of hydroxocobalamin in dogs

• Published in: Journal of neurosurgical anesthesiology Vol. 6; no. 2; p. 111
• Main Authors: de La Coussaye, J E, Houeto, P, Sandouk, P, Levillain, P, Sassine, A, Riou, B
• Format: Journal Article
• Language: English
• Published: United States 01.04.1994
• Subjects: Animals; Dogs; Female; Hydroxocobalamin - administration & dosage; Hydroxocobalamin - pharmacokinetics; Injections, Intravenous; Male
• ISSN: 0898-4921
• DOI: 10.1097/00008506-199404000-00006

Hydroxocobalamin is a powerful cyanide antidote that prevents sodium nitroprusside-induced cyanide toxicity. The pharmacokinetics of an i.v. bolus of hydroxocobalamin (70 and 140 mg/kg) were studied in conscious dogs (n = 6). Plasma hydroxocobalamin concentrations were measured using derivative spectrophotometry. The pharmacokinetics were compatible with a two-compartment model with a first-order distribution and elimination rate, and pharmacokinetic parameters were not different between the two doses, except for the elimination half-life. At 70 mg/kg, which is the recommended dose in acute cyanide poisoning, the elimination half-life was 7.36 +/- 0.79 h, the volume of distribution was 0.49 +/- 0.10 L/kg, and the total clearance 0.58 +/- 0.11 L/h. At high doses, hydroxocobalamin has a short elimination half-life and a limited volume of distribution that exceeds blood volume. These results could be useful in elaborating guidelines for the administration of hydroxocobalamin, when repetitive bolus and/or continuous infusion is required.