Pharmacokinetics of hydroxocobalamin in smoke inhalation victims.
OBJECTIVE
Hydroxocobalamin has been proposed as a cyanide antidote. Little is known, however, about its pharmacokinetics in human cyanide poisoning.


METHODS
We prospectively studied the pharmacokinetics of hydroxocobalamin in 11 smoke inhalation victims of whom all but one had objective evidence of cyanide exposure. Serum hydroxocobalamin levels were followed from just before drug administration to six days after a single 5 g dose of hydroxocobalamin.


RESULTS
The results (mean +/- standard error) suggest a two compartment model. Distribution half-life is on the order of 1.86 +/- 0.34 h and the elimination half-life 26.2 +/- 2.7 h. The apparent volume of distribution is 0.45 +/- 0.03 L/kg. Renal and total body clearance are 0.31 +/- 0.06 and 0.83 +/- 0.07 L/h, respectively.


CONCLUSIONS
The apparent volume of distribution suggests a predominantly extracellular partitioning of the antidote, even in the presence of cyanide, an important factor in terms of its antidotal effect. Hydroxocobalamin's elimination half-life in these cyanide-exposed patients far exceeds those found in previous studies of dogs and minimally-exposed humans. If confirmed, this half-life suggests that a single dose of hydroxocobalamin, sufficiently large enough to bind the cyanide present, should be adequate.
Houeto
P
P
Hôpital Fernand Widal, Université de Paris VII, France.
Borron
S W
SW
Sandouk
P
P
Imbert
M
M
Levillain
P
P
Baud
F J
FJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000931:Antidotes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D003486:Cyanides / Q000037:antagonists & inhibitors / Q000506:poisoning; D005260:Female; D006207:Half-Life; D006801:Humans; D006879:Hydroxocobalamin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015208:Smoke Inhalation Injury / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
D000931:Antidotes; D003486:Cyanides; D003404:Creatinine; D006879:Hydroxocobalamin