Self-Administration of Pralidoxime in Nerve Gas Poisoning with A Note on the Stability of the Drug

Abstract

Plasma concentrations of pralidoxime methane sulphonate (P2S) have been determined in man after self-administration by an automatic injector. After administration of 10 mg./kg. P2S in a 50 per cent w/v solution, concentrations over 4 pg./ml. were reached within 6 min. and maintained for about 90 min. After 20 mg./kg., plasma concentrations over 4 pg./ml. were maintained for about 170 min. Except for pain at the site of injection, which disappeared after a few hr., no serious side reactions could be detected. The drug can be stored for 5 years at 5" with less than 7 per cent decomposition. The decomposition products were found to be less toxic than the unchanged oxime. N-Methylpyridinium-2carboxamide was identified as a major degradation product.

Plasma concentrations of the oxime Pralidoxime Mesylate (P2S) after repeated oral and intramuscular administration.

“…Intramuscular P2S given alone did not produce any ocular side-effects despite plasma P2S levels of 21*4 ,tg/ml (23 5 mg/kg) and 28-9 ,tg/ml (24-6 mg/kg) in two out of nine subjects receiving 3 x 500 mg intramuscular P2S doses. When administered intramuscularly in higher doses in terms of body weight than employed in the study described, no visual effects have been reported despite plasma P2S levels in excess of 20 ,ug/ml (Sundwall, 1960;Calesnick et al, 1967;Barkman et al, 1963) whereas when intramuscular and oral P2S are combined ocular disturbances are reported (Barkman et al, 1963).…”

“…Plasma P2S levels of 12-0 ,ig/ml following 45 mg/kg intramuscularly also produced no clinical effects (Calesnick et al, 1967). Two doses of 750 mg P2S intramuscularly produced no clinical effects but when 750 mg P2S intramuscularly was followed by 2 0 g P2S orally one subject out of nine complained of diplopia (Barkman et al, 1963). In civilian situations where no medical aid is immediately available and in military situations where nerve agent poisoning might occur, the selfadministration of P2S and atropine sulphate by means of a self-injection device (Barkman, 1973;Barkman et al, 1963) has been suggested.…”

“…In emergency situations or where no medical aid is immediately available, its use in this manner might be impractical and therefore immediate administration intramuscularly, possibly by means of self-injection devices (Barkman, Edgren, and 43 Sundwall, 1963;Barkman, 1973) would be more desirable. Measurement of changes in P2S plasma concentration with time following intramuscular administration of a single dose of P2S expressed in terms of body weight, has been carried out by various workers (Sundwall, 1960;Calesnick, Christensen, and Richter, 1967).…”

Pralidoxime mesylate absorption and heart rate response to atropine sulphate following intramuscular administration of solution mixtures.

“…in Sweden however collaboration between Astra Pharmaceuticals and the Swedish military and civil authorities has resulted in the production of a device containing a mixture of the oxime Toxogonin and atropine sulphate (Barkman, Edgren & Sundwall, 1963;Barkman, 1973). The oxime advocated in this country is pralidoxime mesylate (P2S).…”

“…injection of P2S and atropine (Barkman, Edgren & Sundwall, 1963;Barkman, 1973). The oxime advocated in this country is pralidoxime mesylate (P2S).…”