The Utility of Human Plasma-Derived Butyrylcholinesterase (huBuChE) as a Therapeutic Measure in the Absence of Pre-Treatment or Conventional Post-Poisoning Therapies Against Nerve Agent
Abstract
The aim of this study was to demonstrate, in guinea-pigs in vivo, the utility of huBuChE as a therapy against percutaneous (p.c.) nerve agent poisoning, following which there is a slower absorption of agent than by the inhalation route and consequently a longer window of opportunity for therapeutic intervention. The p.c. toxicity of VR was determined in Dunkin- Hartley guinea-pigs. The 24h LD50 was 0.45mg/kg (0.36 0.54 95% CI) and the 48-h LD50 was 0.38 mg/kg (0.31-0.45 95% CI). We used a telemetered guinea-pig model to assess the efficacy of post-exposure therapy using huBuChE. When therapy was administered by the intramuscular (i.m.) route within 2h of VR poisoning (1.6 LD50), high protection levels were achieved; 87.5% (7/8) of guinea-pigs survived to 7 days. Delaying the administration of huBuChE to the onset of systemic cholinergic signs of poisoning dramatically reduced the survival rate to 3/8 animals. Therapy using huBuChE via the intravenous (i.v.) route improved the survival rate compared to therapy via the i.m. route; 7/8 animals survived to the end of the experiment at 7 days. The physiological data suggest that huBuChE acts by preventing or mitigating the detrimental changes seen following p.c. VR exposure, e.g. seizure, hypothermia, bradycardia.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2011
- Accession Number
- ADA553097
Entities
People
- Helen Mumford