Human plasma-derived butyrylcholinesterase is behaviorally safe and effective in cynomolgus macaques (Macaca fascicularis) challenged with soman

Publication date: Available online 24 May 2019Source: Chemico-Biological InteractionsAuthor(s): Todd M. MyersAbstractOrganophosphorus compounds (OP) pose a significant threat. Administration of human butyrylcholinesterase (HuBChE) may reduce or prevent OP toxicity. Thus, we evaluated the safety and efficacy of HuBChE in monkeys using sensitive neurobehavioral tests while concurrently characterizing absorption and elimination in the presence and absence of high-dose soman exposure to predict time course and degree of protection. Eight young adult male cynomolgus macaques were trained on two distinct automated tests of neurobehavioral functioning. HuBChE purified under current Good Manufacturing Practices (CGMP) was injected intramuscularly at 13.1 mg/kg, producing an average peak plasma value (Cmax) of over 27 Units/ml. The apparent time to maximum concentration (Tmax) approximated 7 h, the elimination half-life approximated 102 h, and plasma levels returned to pre-administration (baseline) levels by 14 days. No behavioral disruptions following HuBChE administration were observed on either neurobehavioral test, even in monkeys injected 24 h later with an otherwise lethal dose of soman. Thus, HuBChE provided complete neurobehavioral protection from soman challenge. These data replicate and extend previous results from our laboratory using a different route of administration (intravenous), a different species (rhesus macaque), and a different BChE product (non-CGMP mater...

Source: Chemico Biological Interactions - May 25, 2019 Category: Biochemistry Source Type: research