The effect of oral pyridostigmine bromide on the recovery of whole blood cholinesterase activity following ex vivo exposure to soman

Abstract

Background RBC acetylcholinesterase (AChE) and serum butyrylcholinesterase (BChE) inhibition are considered good biomarkers for protection against exposure to nerve agents. These enzymes may be sequestered (reversibly bound) by pyridostigmine bromide (PB) to protect against the lethal, irreversible binding to organophosphates such as soman (GD). Methods Twenty-four human subjects were given either 30 mg PB orally (n=19) or nothing (n=5). Blood samples were obtained pre- and 2.5, 5, 8, and 24 hours post-dosing. The samples were analyzed for AChE and BChE activity and for PB concentration, using validated spectrophotometric and HPLC/MS methods, respectively. Additionally, the recovery of AChE activity over time following ex vivo exposure of the samples to GD was quantified. Results Maximal inhibition of AChE (29.9%) and concentration of PB (17.1 ng/mL) was noted at 2.5h. AChE activity returned to 95% of pre-dose values at 24h. A linear correlation was found between the amount of PB measured in the blood and the inhibition of AChE. Following GD exposure, recovered AChE activity was similar to levels that were reversibly protected by the PB administration. Conclusion Preliminary data analysis confirms previous findings that PB is an effective pre-treatment drug against soman nerve agent exposure, and that RBC-AChEI is a marker of protection. Complete data and analysis will be presented. Clinical Pharmacology & Therapeutics (2004) 75, P87–P87; doi: 10.1016/j.clpt.2003.11.332