Pharmacokinetics and Immunologic Consequences of Repeated Administrations of Purified Butyrylcholinesterases in Mice
Abstract
Human serum butyrylcholinesterase (Hu BChE) was demonstrated to be an effective prophylaxis that can protect animals from organophosphate nerve agents. However, if the enzyme is to be used in humans, then knowledge of both the pharmacokinetics of the enzyme and its immunological consequences in vivo, is necessary. The present study sought to assess the pharmacokinetics and circulating anti-BChE antibodies produced following repeated administrations of purified Hu BChE and mouse BChE (Mo BChE) in mice. An i.m. injection of 100 U of Hu BChE in Balb/c or CD-1 mice displayed a mean retention time (MRT) of ~50 h, and area under the curve (AUC) of ~1250. The same dose of Mo BChE (purified from sera of CD-1 mice) injected in Balb/c mice exhibited a higher MRT of 78 h and AUC of 1815; the AUC increased to 2504 in CD-1 mice. As expected, a second injection of Hu BChE in mice exhibited a marked reduction in circulatory stability. Although, the second injection of Mo BChE displayed reduced circulatory stability in Balb/c mice, its stability was almost identical to the first injection in CD-1 mice. Consistent with these observations, circulating anti-BChE IgGs were observed in mice injected with Hu BChE and Balb/c mice injected with Mo BChE. No antibody response was detected in CD-1 mice following either injection of homologous Mo BChE. These results bode well for the potential use of human BChE as a detoxifying drug in humans.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 16, 2004
- Accession Number
- ADA449629
Entities
People
- Ashima Saxena
- Bhupendra P. Doctor
- Chunyuan Luo
- Ramachandra S. Naik
- Wei Sun
Organizations
- Walter Reed Army Institute of Research