Meshulam_1995_J.Appl.Toxicol_15_263

This study was designed to evaluate the prophylactic efficacy of transdermally administered physostigmine (PHY) against soman exposure using guinea-pigs. Transdermal PHY pad (3 cm2 kg-1; 60 micrograms cm-2), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 h before exposure to the organophosphate. At the time of exposure, PHY concentrations in brain and plasma were ca. 3.6 ng g-1 and 4.1 ng ml-1, respectively. Brain and whole blood cholinesterase (ChE) activity was inhibited to 70% and 47% of the original activity, respectively. Transdermal PHY by itself protected up to 70% of the animals exposed to 1.5 LD50 of soman (100% mortality was recorded in the control group). Combining transdermal PHY with Scopoderm provided full protection against 1.5 LD50 of soman (protection of 70% against 3 LD50). When the prophylactic treatment was combined with post-exposure therapy (atropine, 10 mg kg-1; toxogonin, 10 mg kg-1) 1 min after 5 LD50 of soman, protection of 90% of the animals was achieved.