CLINICAL STUDY OF A NEW THERAPY FOR NERVE AGENT POISONING: ASCENDING DOSE TOLERANCE STUDY OF HI-6 + ATROPINE

Authors
  1. Clement, J.G.
  2. Madill, H.D.
  3. Bailey, D.
  4. Spence, J.D.
Corporate Authors
Defence Research Establishment Suffield, Ralston ALTA (CAN)
Abstract
The report details a double-blind, placebo controlled, ascending dose tolerance and pharmacokinetic study of HI-6 + atropine sulfate 2 mg in 24 healthy plasma concentrations of 1.88, 4.96, 8.31 and 15.0 mug/mL were found 30-36 min after administration and maintained above 4 mug/mL concentration for 0. 39, 112, and 172.5 min following injection of 62.5, 125, 250, or 500 mg HI-6 + atropine (2 mg), respectively. The calculated half life of HI-6 was 78.2 min following 62.5 mg HI-6 + atropine dose and approximately 64-67 min following 125-500 mg HI-6 + atropine doses. Approximately 50% of the total dose of HI-6 was eliminated unchanged in the urine. There were significant changes (p < 0.05) in AST, CPK, creatinine and gamma GT following the 500 mg HI-6 + atropine dose but they were not considered to be clinically significant. Urinalysis, hematology and semen analysis over the 24 hr observation period was uneventful. There were no cliniclaly significant changes in heart rate or ECG trace, respiration or blood pressure, visual and mental acuity following HI-6 + atropine. The various does of HI-6 + atropine were well tolerated by the subjects as no serious clinical complaints were reported. With the rapid absorption and the lack of clinically significant side effects, combined with the superior efficacy against all nerve agents, HI-6 shows great promise as a replacement oxime in the therapy of nerve agent poisoning.
Keywords
Pharmokinetics;Trials;Cardiac;Eye (anatomy);Serum chemistry;Elimination;Half life;Blood pressure;Blood concentration
Report Number
DRES-597 —
Date of publication
01 Apr 1994
Number of Pages
40
DSTKIM No
94-03752
CANDIS No
143609
Format(s):
Hardcopy;Originator's fiche received by DSIS

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