The oxime HI-6 – Determination of pharmacokinetics and the effect of atropine co-administration in guinea pigs and domestic swine

PDF

Authors
  1. Bohnert, S.T.C.
Corporate Authors
Defence Research and Development Canada, Suffield Research Centre, Ralston AB (CAN)
Abstract
Chemical warfare agents including organophosphorus nerve agents (NA) continue to be a significant threat to both military and civilian populations. The current Canadian Armed Forces (CAF) treatment of NA poisoning includes administration of the oxime HI-6 (used to reactivate inhibited acetylcholinesterase) in combination with atropine contained in an autoinjector, with a benzodiazepine also being administered. Two salts of HI-6 are currently available: HI-6 2Cl (1- [[[4-(Aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydroxyiminio)methyl] pyridinium dichloride (MW 376.22 g/mol) and HI-6 DMS (1-[[[4- (Aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydroxyiminio)methyl] pyridinium dimethanesulfonate (MW 477.49 g/mol). Currently HI-6 is available to the Canadian Armed Forces under a special access program. In order to attain licensure of HI-6 numerous studies must be carried out in animal models to ensure its safety (tolerability and toxicity), efficacy and pharmacokinetics prior to human clinical trials. The present experiment aimed to determine and compare the pharmacokinetic parameters of HI-6 in two animal models under various conditions including: direct comparison of salts (HI-6 2Cl compared to HI-6 DMS), comparison of routes of administration (intramuscular compared to intravenous), comparison of effect of anaesthetic, comparison of different concentrations of HI-6, determination of the effect of atropine sulphate co-administration and evaluation of calculated pharmacokinetic p
Keywords
Oximes;HI-6;Atropine Sulphate;Nerve Agents;Organophosphates
Report Number
DRDC-RDDC-2017-N014 — External Literature
Date of publication
10 Oct 2017
Number of Pages
165
DSTKIM No
CA045171
CANDIS No
805559
Format(s):
Electronic Document(PDF)

Permanent link

Document 1 of 1

Date modified: