Pharmacokinetics of hydroxocobalamin in dogs.
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.
Département d'Anesthésie-Réanimation, CHU de Nîmes, France.
J E
JE
de La Coussaye
P
P
Houeto
P
P
Sandouk
P
P
Levillain
A
A
Sassine
B
B
Riou
D000818:Animals; D004285:Dogs; D005260:Female; D006879:Hydroxocobalamin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male
D006879:Hydroxocobalamin