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

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Authors
  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)
Abstract
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.
Keywords
Soman
Report Number
DRDC-SUFFIELD-SL-2004-111 — Scientific Literature
Date of publication
10 May 2005
Number of Pages
12
Reprinted from
Science Direct, vol 208, 2005, p 399-409
DSTKIM No
CA025803
CANDIS No
523519
Format(s):
Hardcopy;Document Image stored on Optical Disk

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