Rapid and complete bioavailability of antidotes for organophosphorus nerve agent and cyanide poisoning in minipigs after intraosseous administration.
OBJECTIVE
Management of chemical weapon casualties includes the timely administration of antidotes without contamination of rescuers. Personal protective equipment makes intravenous access difficult but does not prevent intraosseous drug administration. We therefore measured the systemic bioavailability of antidotes for organophosphorus nerve agent and cyanide poisoning when administered by the intraosseous, intravenous, and intramuscular routes in a small study of Göttingen minipigs.


METHODS
Animals were randomly allocated to sequentially receive atropine (0.12 mg/kg by rapid injection), pralidoxime (25 mg/kg by injection during 2 minutes), and hydroxocobalamin (75 mg/kg during 10 minutes) by the intravenous or intraosseous route, or atropine and pralidoxime by the intramuscular route. Plasma concentrations were measured for 6 hours to characterize the antidote concentration-time profiles for each route.


RESULTS
Maximum plasma concentrations of atropine and pralidoxime occurred within 2 minutes when administered by the intraosseous route compared with 8 minutes by the intramuscular route. Maximum plasma hydroxocobalamin concentration occurred at the end of the infusion when administered by the intraosseous route. The mean area under the concentration-time curve by the intraosseous route was similar to the intravenous route for all 3 drugs and similar to the intramuscular route for atropine and pralidoxime.


CONCLUSIONS
This study showed rapid and substantial antidote bioavailability after intraosseous administration that appeared similar to that of the intravenous route. The intraosseous route of antidote administration should be considered when intravenous access is difficult.
NPIS Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK.
Douglas B
DB
Murray
Michael
M
Eddleston
Simon
S
Thomas
Robert D
RD
Jefferson
Adrian
A
Thompson
Mick
M
Dunn
Daniel S
DS
Vidler
R Eddie
RE
Clutton
Peter G
PG
Blain
D000818:Animals; D000931:Antidotes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001285:Atropine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D002619:Chemical Warfare Agents / Q000506:poisoning*; D003486:Cyanides / Q000037:antagonists & inhibitors / Q000506:poisoning*; D006879:Hydroxocobalamin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D017148:Infusions, Intraosseous / Q000379:methods*; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D008297:Male; D062025:Organophosphate Poisoning / Q000188:drug therapy*; D011220:Pralidoxime Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
D000931:Antidotes; D002619:Chemical Warfare Agents; D003486:Cyanides; D011220:Pralidoxime Compounds; D001285:Atropine; C028797:pralidoxime; D006879:Hydroxocobalamin