concentrations of the oxime Pralidoxime Mesylate (P2S) after repeated oral and intramuscular administration. The use of the oxime P2S as intravenous therapy for organophosphorus anticholinesterase poisoning is well known. In emergency situations this route of administration may prove impractical due to severe symptoms of anticholinesterase poisoning and therefore the intramuscular route is to be preferred. The absolute intramuscular dose of P2S per man, recommended as necessary for adequate therapy of anticholinesterase poisoning, is 500 mg. In practical situations this dose may have to be repeated at intervals resulting in overdosage, and therefore the clinical side-effects which this regimen might have on normal subjects has been determined. It has also been suggested that where organophosphorus anticholinesterase compounds are handled continuously for many months in the year, for example, in crop spraying and in industry, P2S might be taken prophylactically. The effects that such a regimen might have when combined with therapeutic procedures in human subjects have therefore been evaluated. The absolute intramuscular P2S dose of 500 mg when repeated three times at 20-minute intervals in normal subjects produces no clinical sideeffects. However, when this procedure is superimposedupon an oral P2S prophylactic regimen, up to 60% of the individuals complain of visual side-effects which may prove a hazard in cases of mild anticholinesterase poisoning. It is suggested that these visual side-effects are caused by an accumulation of P2S in the eye during prolonged oral administration.
1The oxime pralidoxime mesylate (P2S) and atropine sulphate, alone and mixed, have been administered intramuscularly to forty-four human subjects. Doses of 750 mg and 500 mg P2S and 2.0 mg atropine sulphate were used. 2 The presence of P2S had no significant influence, as judged by effect on heart rate, on the absorption of atropine although there was a tendency for atropine to exert its effects more rapidly when administered mixed with P2S. 3 No significant difference in the rate of uptake of P2S as judged by plasma levels following injection, between a combined (plus atropine) and single (P2S alone) intramuscular injection was found.
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