Accession Number:

ADA539561

Title:

Butyrylcholinesterase as a Therapeutic Drug for Protection Against Percutaneous VX

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Report Date:

2010-01-01

Pagination or Media Count:

5.0

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. 1 h after a percutaneous exposure of guinea pigs to either 2xLD50 or 5xLD50 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.

Subject Categories:

  • Biochemistry
  • Pharmacology
  • Organic Chemistry
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE