Changes in blood pressure after administration of hydroxocobalamin: Relationship to changes in plasma cobalamins-(III) concentrations in healthy volunteers

Abstract

Objective. To assess the relationship between blood pressure changes following infusion of antidotal doses of hydroxocobalamin and plasma concentrations of total and free cobalamins-(III). Methods. Independent groups of healthy volunteers received single intravenous doses of 2.5, 5, 7.5, or 10 g hydroxocobalamin over 7.5 to 30 minutes. Results. In the pharmacokinetic population (n = 41), hydroxocobalamin caused short-lived mean blood pressure increases. Blood pressure increased shortly after initiation of infusion and returned nearly to baseline by 4 hours post-infusion. The time course of blood pressure changes coincided with that of changes in plasma total and free cobalamins-(III). Change in mean arterial pressure (MAP) was strongly correlated with plasma area-under-the-concentration-time curves (AUCs) of total and free cobalamins-(III) during infusion (r > 0.7) but not through 24 hours post-infusion (r ≤ 0.36). Conclusion. The short-lived increase in mean blood pressure during administration of antidotal doses of hydroxocobalamin is closely linked to initial exposure to total and free cobalamins-(III).

Keywords: :

• Cyanide
• Antidote
• Pharmacodynamics

Acknowledgments

This study was funded by EMD Pharmaceuticals, an affiliate of Merck KGaA, Darmstadt, Germany. The authors are employees of Merck KGaA. The authors acknowledge Jane Saiers, PhD, for assistance with writing this article. Dr. Saiers' work was funded by Dey, L.P., an affiliate of Merck KGaA, Darmstadt, Germany.