Characterization of equine butyrylcholinesterase disposition in the mouse.
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.
Koetzner
Lee
L
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-0632, USA.
Woods
James H
JH
D000818:Animals; D001212:Asialoglycoproteins / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000493:pharmacokinetics*; D003042:Cocaine / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D060748:Fetuins; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009043:Motor Activity / Q000187:drug effects; D014018:Tissue Distribution; D000509:alpha-Fetoproteins / Q000494:pharmacology
D001212:Asialoglycoproteins; D060748:Fetuins; D000509:alpha-Fetoproteins; C017029:asialofetuin; D002091:Butyrylcholinesterase; D003042:Cocaine