Changes in blood pressure after administration of hydroxocobalamin: relationship to changes in plasma cobalamins-(III) concentrations in healthy volunteers.
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 < or = 0.36).


CONCLUSIONS
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).
Uhl
Wolfgang
W
Merck KGaA, Darmstadt, Germany. wolfgang.uhl@merck.de
Nolting
Arno
A
Gallemann
Dieter
D
Hecht
Stefan
S
Kovar
Andreas
A
D000328:Adult; D000931:Antidotes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006879:Hydroxocobalamin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011041:Poisoning / Q000188:drug therapy; D013997:Time Factors; D014805:Vitamin B 12 / Q000097:blood*
D000931:Antidotes; D014805:Vitamin B 12; D006879:Hydroxocobalamin