HYDROXOCOBALAMIN AS A CYANIDE ANTIDOTE - SAFETY, EFFICACY AND PHARMACOKINETICS IN HEAVILY SMOKING NORMAL VOLUNTEERS

The safety, efficacy and pharmacokinetic parameters of 5 g of hydroxoc obalamin given intravenously, alone or in combination with 12.5 g of s odium thiosulfate, were evaluated in healthy adult men who were heavy smokers. Sodium thiosulfate caused nausea, vomiting, and localized bur ning, muscle cramping, or twitching at the infusion site. Hydroxocobal amin was associated with a transient reddish discoloration of the skin , mucous membranes, and urine, and when administered alone produced me an elevations of 13.6% in systolic and 25.9% in diastolic blood pressu re, with a concomitant 16.3% decrease in heart rate. No other clinical ly significant adverse effects were noted. Hydroxocobalamin alone decr eased whole blood cyanide levels by 59% and increased urinary cyanide excretion. Pharmacokinetic parameters of hydroxocobalamin were best de fined in the group who received both antidotes: t1/2 (alpha), 0.52 h; t1/2 (beta), 2.83 h; Vd (beta), 0.24 L/kg; and mean peak serum concent ration 753 mcg/mL (560 mumol/L) at 0-50 minutes after completion of in fusion. Hydroxocobalamin is safe when administered in a 5 gram intrave nous dose, and effectively decreases the low whole blood cyanide level s found in heavy smokers.