RT Journal Article
SR Electronic
T1 Butyrylcholinesterase Accelerates Cocaine Metabolism: In Vitro and In Vivo Effects in Nonhuman Primates and Humans
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 367
OP 371
VO 28
IS 3
A1 Carmona, Gilberto N.
A1 Jufer, Rebecca A.
A1 Goldberg, Steven R.
A1 Gorelick, David A.
A1 Greig, Nigel H.
A1 Yu, Qian-Sheng
A1 Cone, Edward J.
A1 Schindler, Charles W.
YR 2000
UL http://dmd.aspetjournals.org/content/28/3/367.abstract
AB Butyrylcholinesterase (BChE) is known to metabolize cocaine in humans. In the present study, three different experiments were performed to determine whether the addition of horse serum-derived BChE would accelerate the metabolism of cocaine. In the first experiment, the addition of BChE to squirrel monkey plasma in vitro reduced the half-life of cocaine by over 80%, decreased the production of the metabolic product benzoylecgonine, and increased ecgonine methyl ester formation. The effect of BChE on cocaine metabolism was reversed by a specific BChE inhibitor. In the second, in vivo, experiment, exogenously administered BChE reduced peak cocaine concentrations when given to anesthetized squirrel monkeys. Finally, incubation of cocaine with added BChE in human plasma in vitro resulted in a decrease in cocaine half-life similar to that observed with squirrel monkey plasma. The magnitude of the decrease in cocaine half-life was proportional to the amount of added BChE. Together, these results indicate that exogenously administered BChE can accelerate cocaine metabolism in such a way as to potentially lessen the behavioral and toxic effects of cocaine. Therefore, BChE may be useful as a treatment for cocaine addiction and toxicity.