Biochemical, molecular and preclinical characterization of a double-virus-reduced human butyrylcholinesterase preparation designed for clinical use
Author(s)
Weber, A
Butterweck, H
Mais-Paul, U
Teschner, W
Lei, L
Muchitsch, E-M
Kolarich, D
Altmann, F
Ehrlich, HJ
Schwarz, HP
Griffith University Author(s)
Year published
2011
Metadata
Show full item recordAbstract
Background and Objectives: A human plasma-derived butyrylcholinesterase preparation manufactured on the industrial scale is described.
Material and Methods: The human butyrylcholinesterase (hBChE) product was extensively investigated for its purity using immunological and electrophoretic methods and characterized by thorough glycoproteomic approaches. A comprehensive preclinical testing programme addressing safety and pharmacokinetic parameters supplemented the biochemical characterization.
Results: The high-purity hBChE preparation is tetrameric and has high specific activity and molecular integrity of the protein ...
View more >Background and Objectives: A human plasma-derived butyrylcholinesterase preparation manufactured on the industrial scale is described. Material and Methods: The human butyrylcholinesterase (hBChE) product was extensively investigated for its purity using immunological and electrophoretic methods and characterized by thorough glycoproteomic approaches. A comprehensive preclinical testing programme addressing safety and pharmacokinetic parameters supplemented the biochemical characterization. Results: The high-purity hBChE preparation is tetrameric and has high specific activity and molecular integrity of the protein backbone. Acute toxicity studies and in vivo thrombogenicity studies provided evidence of a sufficient safety margin for use in humans. Conclusion: Extensive preclinical safety and pharmacokinetic testing confirmed that this hBChE preparation can be used for further efficacy testing as a bioscavenger for toxic organophosphate compounds in appropriate animal models and ultimately in humans.
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View more >Background and Objectives: A human plasma-derived butyrylcholinesterase preparation manufactured on the industrial scale is described. Material and Methods: The human butyrylcholinesterase (hBChE) product was extensively investigated for its purity using immunological and electrophoretic methods and characterized by thorough glycoproteomic approaches. A comprehensive preclinical testing programme addressing safety and pharmacokinetic parameters supplemented the biochemical characterization. Results: The high-purity hBChE preparation is tetrameric and has high specific activity and molecular integrity of the protein backbone. Acute toxicity studies and in vivo thrombogenicity studies provided evidence of a sufficient safety margin for use in humans. Conclusion: Extensive preclinical safety and pharmacokinetic testing confirmed that this hBChE preparation can be used for further efficacy testing as a bioscavenger for toxic organophosphate compounds in appropriate animal models and ultimately in humans.
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Journal Title
Vox Sanguinis
Volume
100
Issue
3
Subject
Clinical sciences
Clinical sciences not elsewhere classified
Medical physiology