The pharmacology of cocaethylene in humans following cocaine and ethanol administration

• Published in: Drug and alcohol dependence 2003-11, Vol.72 (2), p.169-182
• Main Authors: Harris, Debra S, Everhart, E.Thomas, Mendelson, John, Jones, Reese T
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adult; Adult and adolescent clinical studies; Biological and medical sciences; Blood Pressure - drug effects; Chromatography; Cocaethylene; Cocaine; Cocaine - administration & dosage; Cocaine - analogs & derivatives; Cocaine - blood; Cocaine - pharmacokinetics; Cocaine - urine; Cross-Over Studies; Dopamine Uptake Inhibitors - blood; Dopamine Uptake Inhibitors - pharmacology; Dopamine Uptake Inhibitors - urine; Dose-Response Relationship, Drug; Double-Blind Method; Drug addiction; Drug addictions; Drug Interactions; Ethanol; Ethanol - administration & dosage; Ethanol - blood; Ethanol - pharmacokinetics; Ethanol - urine; Ethyl alcohol; Female; Heart Rate - drug effects; Humans; Male; Medical sciences; Metabolic Clearance Rate; Pharmacokinetics; Pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Toxicology
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/S0376-8716(03)00200-X

Background: Concurrent use of cocaine and alcohol results in formation of a cocaine homolog and metabolite—cocaethylene. Methods: To characterize cocaethylene pharmacology, ten paid volunteer subjects were given deuterium-labeled (d 5) cocaine (0.3, 0.6, and 1.2 mg/kg and cocaine placebo) by a 15-min constant rate intravenous injection 1 h after a single oral dose of ethanol (1 g/kg) or ethanol and cocaine placebo using a double-blind, crossover design. Six of the same volunteers subsequently received a 1.2 mg/kg dose of cocaine alone. A small (7.5 mg) nonpharmacologically active dose of deuterium-labeled cocaethylene-d 3 was concurrently administered with the cocaine to enable calculation of absolute cocaethylene formation and clearance. Plasma and urine cocaine, cocaethylene, and benzoylecgonine concentrations, physiologic and subjective effects were measured. Results: When co-administered with ethanol, 17±6% (mean±S.D.) of the cocaine was converted to cocaethylene. Cocaethylene peak plasma concentrations and AUC increased proportionally to the cocaine dose. Ethanol ingestion prior to cocaine administration decreased urine benzoylecgonine levels by 48% and increased urinary cocaethylene and ecgonine ethyl ester levels. Subjects liked and experienced more total intoxication after the combination of cocaine and ethanol than after either drug alone. Conclusions: In the presence of ethanol, the altered biotransformation of cocaine resulted in 17% of an intravenous cocaine dose being converted to cocaethylene and relatively lower urinary concentrations of benzoylecgonine.