The effect of ethanol on oral cocaine pharmacokinetics reveals an unrecognized class of ethanol-mediated drug interactions.

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Robert B Parker, S Casey Laizure

Abstract

Ethanol decreases the clearance of cocaine by inhibiting the hydrolysis of cocaine to benzoylecgonine and ecgonine methyl ester by carboxylesterases, and there is a large body of literature describing this interaction as it relates to the abuse of cocaine. In this study, we describe the effect of intravenous ethanol on the pharmacokinetics of cocaine after intravenous and oral administration in the dog. The intent is to determine the effect ethanol has on metabolic hydrolysis using cocaine metabolism as a surrogate marker of carboxylesterase activity. Five dogs were administered intravenous cocaine alone, intravenous cocaine after ethanol, oral cocaine alone, and oral cocaine after ethanol on separate study days. Cocaine, benzoylecgonine, and cocaethylene concentrations were determined by high-performance liquid chromatography. Cocaine had poor systemic bioavailability with an area under the plasma concentration-time curve that was approximately 4-fold higher after intravenous than after oral administration. The coadministration of ethanol and cocaine resulted in a 23% decrease in the clearance of intravenous cocaine and a 300% increase in the bioavailability of oral cocaine. Cocaine behaves as a high extraction drug, which und...Continue Reading

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Citations

Oct 30, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kennerly S PatrickRobert J Malcolm
Sep 16, 2010·Expert Opinion on Drug Metabolism & Toxicology·S Casey Laizure, Robert B Parker
Dec 17, 2014·Clinical Pharmacokinetics·Robert B ParkerS Casey Laizure
Feb 21, 2018·Journal of Analytical Toxicology·Marion A CoeSharon L Walsh
Sep 25, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jianmei WuJing Li
Nov 2, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hugues ChanteuxJean-Marie Nicolas
Nov 12, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·S Casey LaizureZhe-Yi Hu
May 14, 2011·Therapeutic Drug Monitoring·Aniket NatekarGideon Koren
Mar 15, 2012·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Carole EvansPatricia Watson
Oct 4, 2020·Forensic Science International : Synergy·Virginia A HillG Neil Stowe

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