Post-exposure
nerve agent treatment usually includes administration of an
oxime, which acts to restore function of the
enzyme acetylcholinesterase (AChE). For immediate treatment of military personnel, this is usually administered with an autoinjector device, or devices containing the
oxime such as
pralidoxime,
atropine and
diazepam. In addition to the autoinjector, it is likely that personnel exposed to
nerve agents, particularly by the percutaneous route, will require further treatment at medical facilities. As such, there is a need to understand the relationship between dose rate, plasma concentration, reactivation of AChE activity and efficacy, to provide supporting evidence for
oxime infusions in
nerve agent poisoning. Here, it has been demonstrated that
intravenous infusion of
HI-6, in combination with
atropine, is efficacious against a percutaneous
VX challenge in the conscious male Dunkin-Hartley guinea-pig. Inclusion of
HI-6, in addition to
atropine in the treatment, improved survival when compared to
atropine alone. Additionally, erythrocyte AChE activity following
poisoning was found to be dose dependent, with an increased dose rate of
HI-6 (0.48mg/kg/min) resulting in increased AChE activity. As far as we are aware, this is the first study to correlate the pharmacokinetic profile of
HI-6 with both its pharmacodynamic action of reactivating
nerve agent inhibited AChE and with its efficacy against a persistent
nerve agent exposure challenge in the same conscious animal.