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The pharmacology of cocaethylene in humans following cocaine and ethanol administration
(Pharmacocinétique du cocaethylène chez l'homme après administration de cocaïne et d'éthanol)
Auteur(s) :
D. S. HARRIS ;
EVERHART E. T. ;
J. MENDELSON ;
R. T. JONES
Article en page(s) :
169-182
Refs biblio. :
39
Domaine :
Drogues illicites / Illicit drugs
Langue(s) :
Anglais
Discipline :
PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods)
Thésaurus mots-clés
COCAINE
;
ALCOOL
;
METABOLITE
;
PHARMACOCINETIQUE
;
INTERACTION CHIMIQUE
;
DOSE-REPONSE
Note générale :
Drug and Alcohol Dependence, 2003, 72, (2), 169-182
Note de contenu :
fig. ; tabl.
Résumé :
ENGLISH :
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 (d5) 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-d3 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 t 6% (mean f 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. (Review's abstract.)
ENGLISH :
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 (d5) 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-d3 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 t 6% (mean f 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. (Review's abstract.)
Affiliation :
Drug Depend. Res. Ctr, L. Porter Psychiatr. Inst., Univ. California, 4001 Parnassus Ave., San Francisco, CA 94143-0984
Etats-Unis. United States.
Etats-Unis. United States.
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