Evaluating the Behavioral and Physiological Safety of Human Butyrylcholinesterase in Rhesus Monkeys
Abstract
We evaluated a large dose of human butyrylcholinesterase (Hu-BChE) in rhesus monkeys using a complex cognitive test (serial-probe recognition, SPR) designed to assess attention and short-term memory. Concurrent with the cognitive-behavioral assessment, blood was collected at critical points throughout the study and was analyzed for AChE and BChE activity, anti-BChE (antibody) activity, and gross clinical pathology (i.e., complete blood count and CHEM 20 panel). Each monkey received an injection of 150 mg (105,000 U or 32 mg/kg) of Hu-BChE 60 min prior to testing on the SPR task. No cognitive-behavioral decrements of any kind were detected in SPR performance and no robust or consistent signs of clinical pathology were detected in any of the blood assays during the 5 weeks of observation. The pharmacokinetics of intravenous Hu-BChE administration revealed a peak in BChE of 226 U/ml at 5 minutes post injection and a mean residence time of approximately 72 hours. These results provide strong support for the behavioral and physiological safety of Hu-BChE in rhesus monkeys.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2005
- Accession Number
- ADA449760
Entities
People
- Ashima Saxena
- Bhuphendra P. Doctor
- Matthew G. Clark
- Reeta Bansal
- Todd M. Myers
- Wei Sun
Organizations
- Walter Reed Army Institute of Research