The Pharmacokinetics and Pharmacodynamics of Two HI-6 Salts in Swine and Efficacy in the Treatment of GF and Soman Poisoning


  1. Lundy, P.M.
  2. Hill, I.
  3. Lecavalier, P.
  4. Hamilton, M.G.
  5. Vair, C.
  6. Davidson, C.
  7. Weatherby, K.L.
  8. Berger, B.J.
Corporate Authors
Defence R&D Canada - Suffield, Ralston ALTA (CAN)
Anesthetized pigs were injected i.m. with 500 mg HI-6 dichloride (HI-6 2CI) (1-[[[4-(aminocarbonyl)-pyridinio]methoxy]methyl]-2[(hydroxyimino)methyl]pyridinium; CAS 34433-31-3)) or the molar equivalent of HI-6 dimethane-sulphonate (HI-6 DMS) 633 mg. Plasma HI-6 concentrations were measured by HPLC (1,3,5,10,15,30,60 min and every 30 min until 4h or 6h following the i.v. or i.m. dose respectively) while a variety of physiological responses were continuously examined. HI-6 (500 mg 2CI or 633 mg DMS) resulted in an identical pharacokinetic profile unaffected by atropine co-administration. Neither HI-6 salt resulted in clinically significant changes in cardiovascular or respiratory function. HI-6 DMS (1899 mg i.v.) resulted in plasma HI-6 concentrations about 10 times higher than measured following i.m. 500 mg 2CI or 633 mg DMS and resulted in small transitory effect on mean arterial pressure. Atropine plus HI-6 DMS (1-9 mg/kg or 127-172 mg/kg i.m.) protected up to 100% of guinea pig exposed to 5 x LD sub 50 of GF (cyclohexyl methyl phosphonoflouridate) or soman (pinacolyl methylphosphonofluoridate) (GD) respectively. The results suggest that the two HI-6 salts have a similar pharmacokinetic profile while HI-6 DMS appears extremely safe and effective against nerve agents and may be as suitable for human use.
Report Number
DRDC-SUFFIELD-SL-2004-111 — Scientific Literature
Date of publication
10 May 2005
Number of Pages
Reprinted from
Science Direct, vol 208, 2005, p 399-409
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