Safety and pharmacokinetics of human serum butyrylcholinesterase in guinea pigs.
Human serum butyrylcholinesterase (Hu BChE) has been demonstrated to be a highly effective detoxifying enzyme for counteracting the acute toxicity of organophosphorus (OP) nerve agents. In order to initiate an investigational new drug (IND) application for human use, the safety and pharmacokinetic properties of the enzyme were assessed in guinea pigs. Sixty milligrams per kilogram of Hu BChE was administered to guinea pigs by either i.p. or i.m. injection. Blood was drawn at various time points for up to 2 weeks following enzyme injection for the measurement of blood BChE activity. Hu BChE displayed a mean residence time of 110 h, regardless of the route of administration and the enzyme activity remained almost 10-fold above baseline level even after 2 weeks post enzyme injection. Fourteen days post Hu BChE administration, all animals were subjected to 20 panel serum chemistry, hematology, and complete gross/histopathology examination. Results showed no toxic effects as measured by general observation, serum chemistry, hematology, and gross and histological tissue changes. In conclusion, Hu BChE displays a long-lasting stability in the circulation of guinea pigs, and is devoid of any toxic side effects. These results provide convincing data for the safe and effective use of Hu BChE as a bioscavenger to protect humans against all OP nerve agents.
Sun
Wei
W
Division of Biochemistry, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA. wei.sun@na.amedd.army.mil <wei.sun@na.amedd.army.mil>
Doctor
B P
BP
Saxena
Ashima
A
D000818:Animals; D002091:Butyrylcholinesterase / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D006801:Humans
D002091:Butyrylcholinesterase