PHARMACOKINETICS OF HYDROXOCOBALAMIN IN DOGS

Hydroxocobalamin is a powerful cyanide antidote that prevents sodium n itroprusside-induced cyanide toxicity. The pharmacokinetics of an i.v. bolus of hydroxocobalamin (70 and 140 mg/kg) were studied in consciou s dogs (n = 6). Plasma hydroxocobalamin concentrations were measured u sing derivative spectrophotometry. The pharmacokinetics were compatibl e with a two-compartment model with a first-order distribution and eli mination rate, and pharmacokinetic parameters were not different betwe en the two doses, except for the elimination half-life. At 70 mg/kg, w hich is the recommended dose in acute cyanide poisoning, the eliminati on 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 dose s, hydroxocobalamin has a short elimination half-life and a limited vo lume of distribution that exceeds blood volume. These results could be useful in elaborating guidelines for the administration of hydroxocob alamin, when repetitive bolus and/or continuous infusion is required.