Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • 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
  • Submit
  • 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
    • Special Sections
    • 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
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

CHARACTERIZATION OF RAT SMALL INTESTINAL AND COLON PRECISION-CUT SLICES AS AN IN VITRO SYSTEM FOR DRUG METABOLISM AND INDUCTION STUDIES

Esther G. van de Kerkhof, Inge A. M. de Graaf, Marina H. de Jager, Dirk K. F. Meijer and Geny M. M. Groothuis
Drug Metabolism and Disposition November 2005, 33 (11) 1613-1620; DOI: https://doi.org/10.1124/dmd.105.005686
Esther G. van de Kerkhof
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Inge A. M. de Graaf
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marina H. de Jager
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dirk K. F. Meijer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Geny M. M. Groothuis
  • 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

The aim of this study was to characterize rat small intestinal and colon tissue slices as a tool to study intestinal metabolism and to investigate gradients of drug metabolism along the intestinal tract as well as drug-induced inhibition and induction of biotransformation. Tissue morphology and the intestinal mucus layer remained intact in small intestinal and colon slices during 3 h of incubation, while alkaline phosphatase was retained and the rate of metabolism of three model compounds (7-hydroxycoumarin, 7-ethoxycoumarin, and testosterone) appeared constant. Phase I and phase II metabolic gradients, decreasing from stomach toward colon were shown to be clearly different for the model compounds used. Furthermore, the observed slice activities were similar or even higher compared with the literature data concerning metabolism of in vitro intestinal systems. Preincubation with β-naphthoflavone for 24 h induced the O-deethylation of 7-ethoxycoumarin from nearly undetectable to 140 pmol/min/mg protein in small intestine (fresh slices, 43 pmol/min/mg protein) and to 100 pmol/min/mg protein in colon slices (fresh slices, undetectable). Ketoconazole inhibited metabolism of testosterone by 40% and that of 7-ethoxycoumarin by 100%. In conclusion, we showed that the intestinal slice model is an excellent model to study drug metabolism in the intestine in vitro, since we found that the viability parameters remain constant and the measured enzyme activities are relevant, sensitive to inhibitors, and inducible. Therefore, it is a promising tool to study intestinal drug metabolism in human intestine in vitro in the future.

Footnotes

  • This study is supported by the Technology Foundation STW, Applied Science Division of NWO and the Technology Programme of the Ministry of Economic Affairs, and Yamanouchi Europe.

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

  • doi:10.1124/dmd.105.005686.

  • ABBREVIATIONS: AP, alkaline phosphatase; TT, testosterone; TOH, hydroxytestosterone; 7HC, 7-hydroxycoumarin; 7HC-GLUC, 7-hydroxycoumarin glucuronide; 7HC-SULF, 7-hydroxycoumarin sulfate; 7EC, 7-ethoxycoumarin; 17β-HSD, 17β-hydroxysteroid dehydrogenase; βNF, β-naphthoflavone; DMSO, dimethyl sulfoxide; KT, ketoconazole; HPLC, high-performance liquid chromatography.

    • Received May 24, 2005.
    • Accepted July 27, 2005.
  • 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: 33 (11)
Drug Metabolism and Disposition
Vol. 33, Issue 11
1 Nov 2005
  • Table of Contents
  • About the Cover
  • Index by author
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.
CHARACTERIZATION OF RAT SMALL INTESTINAL AND COLON PRECISION-CUT SLICES AS AN IN VITRO SYSTEM FOR DRUG METABOLISM AND INDUCTION STUDIES
(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

CHARACTERIZATION OF RAT SMALL INTESTINAL AND COLON PRECISION-CUT SLICES AS AN IN VITRO SYSTEM FOR DRUG METABOLISM AND INDUCTION STUDIES

Esther G. van de Kerkhof, Inge A. M. de Graaf, Marina H. de Jager, Dirk K. F. Meijer and Geny M. M. Groothuis
Drug Metabolism and Disposition November 1, 2005, 33 (11) 1613-1620; DOI: https://doi.org/10.1124/dmd.105.005686

Citation Manager Formats

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

Share
Research ArticleArticle

CHARACTERIZATION OF RAT SMALL INTESTINAL AND COLON PRECISION-CUT SLICES AS AN IN VITRO SYSTEM FOR DRUG METABOLISM AND INDUCTION STUDIES

Esther G. van de Kerkhof, Inge A. M. de Graaf, Marina H. de Jager, Dirk K. F. Meijer and Geny M. M. Groothuis
Drug Metabolism and Disposition November 1, 2005, 33 (11) 1613-1620; DOI: https://doi.org/10.1124/dmd.105.005686
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • A PBPK model for CBD in adults and children
  • Antibiotics Induce Changes in the Expression of Rat DPGs
  • Metabolism of Efavirenz by P450s and UGTs in the Brain
Show more Articles

Similar Articles

Advertisement
  • 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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics