Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

The Effect of Ethanol on Oral Cocaine Pharmacokinetics Reveals an Unrecognized Class of Ethanol-Mediated Drug Interactions

Robert B. Parker and S. Casey Laizure
Drug Metabolism and Disposition February 2010, 38 (2) 317-322; DOI: https://doi.org/10.1124/dmd.109.030056
Robert B. Parker
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Casey Laizure
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

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 undergoes first-pass metabolism in the intestines and liver that is profoundly inhibited by ethanol. We infer from these results that ethanol could inhibit the hydrolysis of other drug compounds subject to hydrolysis by carboxylesterases. Indeed, there are numerous commonly prescribed drugs with significant carboxylesterase-mediated metabolism such as enalapril, lovastatin, irinotecan, clopidogrel, prasugrel, methylphenidate, meperidine, and oseltamivir that may interact with ethanol. The clinical significance of the interaction of ethanol with specific drugs subject to carboxylesterase hydrolysis is not well recognized and has not been adequately studied.

Footnotes

  • This work was supported by the National Institutes of Health National Heart, Lung, and Blood Institute [Grant R15HL54311].

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.109.030056

  • CES1
    carboxylesterase 1
    CES2
    carboxylesterase 2
    BE
    benzoylecgonine
    EME
    ecgonine methyl ester
    AUC
    area under the plasma concentration-time curve.

    • Received August 31, 2009.
    • Accepted November 13, 2009.
  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 38 (2)
Drug Metabolism and Disposition
Vol. 38, Issue 2
1 Feb 2010
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
The Effect of Ethanol on Oral Cocaine Pharmacokinetics Reveals an Unrecognized Class of Ethanol-Mediated Drug Interactions
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

The Effect of Ethanol on Oral Cocaine Pharmacokinetics Reveals an Unrecognized Class of Ethanol-Mediated Drug Interactions

Robert B. Parker and S. Casey Laizure
Drug Metabolism and Disposition February 1, 2010, 38 (2) 317-322; DOI: https://doi.org/10.1124/dmd.109.030056

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

The Effect of Ethanol on Oral Cocaine Pharmacokinetics Reveals an Unrecognized Class of Ethanol-Mediated Drug Interactions

Robert B. Parker and S. Casey Laizure
Drug Metabolism and Disposition February 1, 2010, 38 (2) 317-322; DOI: https://doi.org/10.1124/dmd.109.030056
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Candesartan glucuronide serves as a CYP2C8 inhibitor
  • Role of AADAC on eslicarbazepine acetate hydrolysis
  • Gene expression profile of human intestinal epithelial cells
Show more Articles

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics