Bioscavenger is effective as a delayed therapeutic intervention following percutaneous VX poisoning in the guinea-pig

The prolonged systemic exposure that follows skin contamination with low volatility nerve agents, such as VX, requires treatment to be given over a long time due to the relatively short half-lives of the therapeutic compounds used. Bioscavengers, such as butyrylcholinesterase (BChE), have been shown to provide effective post-exposure protection against percutaneous nerve agent when given immediately on signs of poisoning and to reduce reliance on additional treatments. In order to assess the benefits of administration of bioscavenger at later times, its effectiveness was assessed when administration was delayed for 2 h after the appearance of signs of poisoning in guinea-pigs challenged with VX (4 × LD50). VX-challenged animals received atropine, HI-6 and avizafone on signs of poisoning and 2 h later the same combination with or without bioscavenger. Five out of 6 animals which received BChE 2 h after the appearance of signs of poisoning survived to the end of the study at 48 h, compared with 6 out of 6 which received BChE immediately on signs. All the animals (n = 6 + 6) that received only MedCM, without the addition of BChE, died within 10 h of poisoning. The toxicokinetics of a sub-lethal challenge of percutaneous VX were determined in untreated animals. Blood VX concentration peaked at approximately 4 h after percutaneous dosing with 0.4 × LD50; VX was still detectable at 36 h and had declined to levels below the lower limit of quantification (10 pg/mL) by 48 h in 7 of 8 animals, with the remaining animal having a concentration of 12 pg/mL. These studies confirm the persistent systemic exposure to nerve agent following percutaneous poisoning and demonstrate that bioscavenger can be an effective component of treatment even if its administration is delayed.