HI-6 in man: efficacy of the oxime in poisoning by organophosphorus insecticides.

The efficacy of the oxime HI-6 was studied as a treatment for organophosphorus poisoning. HI-6 was given four times daily as a single intramuscular injection of 500 mg accompanied by atropine and diazepam therapy. Oxime treatment was started on admission and continued for a minimum of 48 h and a maximum of 7 d. HI-6 rapidly reactivated human blood acetylcholinesterase inhibited by dimethoxy organophosphorus compounds, while the dimethoxy-inhibited enzyme was mainly resistant to the treatment by HI-6. Although both HI-6 and pralidoxime chloride reactivated the red blood cell cholinesterase in quinalphos-poisoned subjects, the return of enzyme activities was more rapid following the use of HI-6. The general improvement of poisoned patients, which was sometimes more rapid than the rise of acetylcholinesterase activity, pointed to direct pharmacological effects of HI-6. No undesirable side-effects were noted in patients when HI-6 plasma concentrations were maintained at levels far above the 'therapeutic' concentration for up to 7 d.

[Acute poisoning by herbicide compounds]. / Akutna trovanja herbicidima.

The increasing incidence of human poisoning by herbicides arises either from their wide (and sometimes irrational) agricultural use or abuse for suicidal (rarely homicdal) purposes. From the viewpoint of clinical toxicology the intoxisations by dipyrridiles, dinitrophenols and dervivates of phenoxysarbonic acids are of great importance. Due to high acute toxicity of these herbicide compounds accidental or intentional poisonings are mainly characterized by serious morphological damages and complex functional disorders of almost all parenchimatous organs. In spite of urgent treatment and intensive care measures the mortality rate in these intoxications is still high. Based on personal clinical experience in herbicide intoxication and data from literature, the mechanisms of their action, clinical features, current treatment regimen and prognostic elements are reviewed.

HI-6 in man: blood levels, urinary excretion, and tolerance after intramuscular administration of the oxime to healthy volunteers.

After intramuscular administration of graded doses of HI-6 (62.5, 125, 250, and 500 mg) to 22 healthy men, it has been established that therapeutic concentrations of the oxime in plasma, arbitrarily taken as 4 micrograms/ml, were achieved by doses of 250 and 500 mg in about 5 min, and maintained from 2 to 3 hr. The two lowest doses have not been satisfactory in this respect. Of the total doses injected, from 56.3 to 62% of HI-6 was excreted into urine unchanged during the first 6 hr. No side-effects were reported by the subjects, nor revealed by clinical or laboratory tests during the study. Exceptional tolerance of HI-6 in man found in this study, along with its high efficiency proven in experimental poisoning by sarin, VX, and soman, make it the most promising oxime aimed at the treatment of human poisoning by known chemical warfare nerve agents.