Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases
Laizure SC, Mandrell T, Gades NM, Parker RB.
Department of Clinical Pharmacy,
University of Tennessee, Memphis,
Tennessee 38163, USA.
Drug Metab Dispos. 2003 Jan;31(1):16-20


Carboxylesterases are important in the metabolism of cocaine, catalyzing the hydrolysis of cocaine to its two major metabolites, benzoylecgonine and ecgonine methyl ester. In the presence of ethanol, some cocaine undergoes transesterification with ethanol instead of hydrolysis with water producing the active metabolite, cocaethylene. The metabolic fate of cocaethylene is unknown, but given its structural similarity to cocaine, it was hypothesized that cocaethylene would also be metabolized by carboxylesterases and its elimination decreased in the presence of ethanol, as is cocaine's. Dogs were given cocaine alone, cocaethylene alone, cocaine and ethanol, cocaethylene and ethanol, and cocaine and cocaethylene on separate study days and sequential blood samples drawn. Plasma concentrations of cocaine, benzoylecgonine, and cocaethylene were determined by high-performance liquid chromatography. The pharmacokinetic dispositions of cocaine and cocaethylene were similar with clearance values of 0.91 +/- 0.22 and 0.79 +/- 0.16 l/min, and volumes of distribution of 2.6 +/- 0.82 and 2.7 +/- 0.47 l/kg, respectively. Both cocaine and cocaethylene clearances were decreased about 20% when given with ethanol. Following administration of cocaethylene alone, benzoylecgonine achieved similar plasma concentrations as those attained following cocaine alone, which indicates that benzoylecgonine is a major metabolite of cocaethylene. Carboxylesterases play an important role in the elimination of both cocaine and cocaethylene.

Coca alkaloids
Cocaine hotspots
Cocaine withdrawal
The coke-craving brain
The neural basis of addiction
Freebasing flies go hyperkinetic
Cocaine, alcohol and cocaethylene
Cocaethylene and cocaine dependence

01 02 03 04 05 06 07 08 09 10 11 12
13 14 15 16 17 18 19 20 21 22 23 24

Future Opioids
BLTC Research
Wirehead Hedonism
Utopian Pharmacology
The Hedonistic Imperative
When Is It Best To Take Crack Cocaine?

swan image
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family