TY - JOUR
T1 - Characterization of equine butyrylcholinesterase disposition in the mouse
AU - Koetzner, Lee
AU - Woods, James H.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - Butyrylcholinesterase administration has been shown to block the effects of cocaine. However, even in model systems, the pharmacokinetics of the enzyme are only partly understood. Measurements of plasma enzyme concentration, antibody titer determinations, and measurement of cocaine-induced locomotor activity in mice were used to describe the disposition of butyrylcholinesterase. Clearance of the enzyme showed biexponential kinetics; the first component was sensitive to asialofetuin, suggesting a role for the asialoglycoprotein receptor. Cocaine did not influence enzyme disposition. An antibody response to enzyme injection was seen; the role of this response is not clear. The antagonist effect of the enzyme was eliminated faster than the enzyme was eliminated from plasma; this may be due to a contribution of tissue esterases to cocaine metabolism. Intraperitoneal enzyme administration was not effective against cocaine, suggesting that the utility of the enzyme is route-dependent.
AB - Butyrylcholinesterase administration has been shown to block the effects of cocaine. However, even in model systems, the pharmacokinetics of the enzyme are only partly understood. Measurements of plasma enzyme concentration, antibody titer determinations, and measurement of cocaine-induced locomotor activity in mice were used to describe the disposition of butyrylcholinesterase. Clearance of the enzyme showed biexponential kinetics; the first component was sensitive to asialofetuin, suggesting a role for the asialoglycoprotein receptor. Cocaine did not influence enzyme disposition. An antibody response to enzyme injection was seen; the role of this response is not clear. The antagonist effect of the enzyme was eliminated faster than the enzyme was eliminated from plasma; this may be due to a contribution of tissue esterases to cocaine metabolism. Intraperitoneal enzyme administration was not effective against cocaine, suggesting that the utility of the enzyme is route-dependent.
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U2 - 10.1124/dmd.30.6.724
DO - 10.1124/dmd.30.6.724
M3 - Article
C2 - 12019201
AN - SCOPUS:0036259954
VL - 30
SP - 724
EP - 730
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
SN - 0090-9556
IS - 6
ER -