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Chem Biol Interact. 2010 Sep 6;187(1-3):249-52. doi: 10.1016/j.cbi.2010.05.014. Epub 2010 Jun 1.

Butyrylcholinesterase as a therapeutic drug for protection against percutaneous VX.

Author information

1
US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Rd., Aberdeen Proving Ground, MD 21010, United States of America. david.lenz@us.army.mil

Abstract

The administration of purified human plasma-derived butyrylcholinesterase (HuBuChE) as a pretreatment has been demonstrated to enhance survival and protect against decreased cognitive function after exposure to organophosphorus poisons (OPs). Based on efficacy data obtained with guinea pigs and non-human primates and the lack of behavioral side effects, plasma-derived HuBuChE has been granted investigational new drug status by the US Food and Drug Administration. The recent availability of a recombinant form of HuBuChE (rHuBuChE) from the milk of transgenic goats has now allowed us to determine the pharmacokinetics of that material in guinea pigs and use it as a therapy following exposure to the VX. The rHuBuChE was expressed as a dimer and following intramuscular (i.m.) administration had more a rapid adsorption and clearance profile in guinea pigs than the plasma-derived material. Based on those data, we administered rHuBuChE i.m. 1h after a percutaneous exposure of guinea pigs to either 2xLD(50) or 5xLD(50) of VX. Post-exposure therapy with rHuBuChE provided improved survival at both challenge levels, 90% and 33% respectively versus 20% or 0% respectively for animals that did not receive therapy. These studies showed that BuChE can be efficacious as a therapy against percutaneous exposure to VX.

PMID:
20513442
DOI:
10.1016/j.cbi.2010.05.014
[Indexed for MEDLINE]

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