Recent events have brought a clear message to America: both our military and civilian sectors must be ready to deal with mass casualties of chemical and biological agents. In order to provide a more rapidly effective means to treat medical emergencies, Resuscitation Solutions, Inc. has developed FirstMed, an intraosseous auto-injector for self- or buddy-administration of emergency antidotes and drugs. The military and civilian approach to emergency treatment of nerve gas toxicity is the use of small dose intramuscular (IM) auto-injectors as standard of care for rapid self-aid or buddy aid of nerve gas antidotes. This proposal extends this concept to provide a more effective auto-injector with near immediate vascular entry. Vascular uptake of IM injections is likely to be further delayed under conditions of circulatory shock, when hypoperfusion of muscle delays drug uptake. Our research will be the first testing and use of the innovative FirstMed injector for intraosseous (IO) auto-injector administration of time-critical nerve gas antidotes. We hypothesize that IO delivery of nerve gas antidote provides a significant time advantage over the IM route, in the ability to more rapidly achieve therapeutic blood levels after injection and that 10 injector treatment followed by IM injector treatment provides both immediate and sustained circulatory delivery of nerve gas antidote. ? ? We address our hypothesis with two specific aims: 1) measure relative pharmacokinetics of pralidoxime (2-PAM-CI) following IM or IO injection or combined IO injection followed by IM injection in healthy anesthetized normovolemic pigs. 2) evaluate the changes in pharmacokinetics of 2-PAM-CL following IM or IO injection in the compromised circulation of hypovolemic pigs. Intraosseous auto-injector administration of antidotes into red bone marrow is likely to result in significantly better clinical outcomes in severely debilitated victims of chemical agents, organophosphate poisoning or severe anaphylactic reactions. FirstMed IO auto-injectors may provide the most effective initial step in therapy for treatment of soldiers and civilians in the event of exposure to chemical toxins due to weapons or terrorists. ? ?