Effects of ethanol and cocaethylene on cocaine pharmacokinetics in conscious dogs

Coingestion of cocaine and ethanol is common among cocaine users, and this combination is reported to enhance the euphoric effects of cocaine. The cardiovascular effects of cocaine are increased in the presence of ethanol, although the mechanism(s) involved in this interaction are poorly understood. Recent studies suggest the enhanced cardiac effects may be caused by ethanol-mediated inhibition of cocaine metabolism leading to higher cocaine plasma concentrations. However, these studies were all performed in animals or humans that form cocaethylene when ethanol and cocaine are coadministered. Thus, it is also possible that cocaethylene could inhibit cocaine's metabolism. Preliminary studies in our laboratory indicate the dog does not form detectable quantities of cocaethylene after coadministration of cocaine and intravenous ethanol. Thus, the dog may be a useful model for isolating the individual contributions of ethanol and cocaethylene to this interaction. The purpose of the present study was to confirm this observation, and to determine the effects of ethanol and cocaethylene on cocaine pharmacokinetics in the conscious dog. Six dogs received cocaine (3 mg/kg i.v.) alone, ethanol (1 g/kg i.v.) followed by cocaine (3 mg/kg i.v.), and cocaine (3 mg/kg i.v.) + cocaethylene (3 mg/kg i.v.). Cocaethylene was not detected in any of the plasma samples from the six dogs after administration of cocaine and ethanol. Ethanol and cocaethylene reduced mean cocaine clearance by 47% and 26%, respectively. Inhibition of cocaine's metabolism by both ethanol and cocaethylene may play an important role in mediating the enhanced effects of cocaine in the presence of ethanol.