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

Characterization of the Human Intestinal Drug Transport with Ussing Chamber System Incorporating Freshly Isolated Human Jejunum

Kazuyoshi Michiba, Kazuya Maeda, Ko Kurimori, Tsuyoshi Enomoto, Osamu Shimomura, Tomoyo Takeuchi, Hiroyuki Nishiyama, Tatsuya Oda and Hiroyuki Kusuhara
Drug Metabolism and Disposition January 2021, 49 (1) 84-93; DOI: https://doi.org/10.1124/dmd.120.000138
Kazuyoshi Michiba
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (K.Mi., K.Ma., H.K.); Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan (K.K., T.E., O.S., T.O.); and Tsukuba Human Tissue Biobank Center, University of Tsukuba Hospital, Ibaraki, Japan (T.T., H.N.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuya Maeda
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (K.Mi., K.Ma., H.K.); Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan (K.K., T.E., O.S., T.O.); and Tsukuba Human Tissue Biobank Center, University of Tsukuba Hospital, Ibaraki, Japan (T.T., H.N.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ko Kurimori
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (K.Mi., K.Ma., H.K.); Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan (K.K., T.E., O.S., T.O.); and Tsukuba Human Tissue Biobank Center, University of Tsukuba Hospital, Ibaraki, Japan (T.T., H.N.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tsuyoshi Enomoto
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (K.Mi., K.Ma., H.K.); Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan (K.K., T.E., O.S., T.O.); and Tsukuba Human Tissue Biobank Center, University of Tsukuba Hospital, Ibaraki, Japan (T.T., H.N.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Osamu Shimomura
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (K.Mi., K.Ma., H.K.); Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan (K.K., T.E., O.S., T.O.); and Tsukuba Human Tissue Biobank Center, University of Tsukuba Hospital, Ibaraki, Japan (T.T., H.N.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tomoyo Takeuchi
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (K.Mi., K.Ma., H.K.); Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan (K.K., T.E., O.S., T.O.); and Tsukuba Human Tissue Biobank Center, University of Tsukuba Hospital, Ibaraki, Japan (T.T., H.N.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroyuki Nishiyama
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (K.Mi., K.Ma., H.K.); Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan (K.K., T.E., O.S., T.O.); and Tsukuba Human Tissue Biobank Center, University of Tsukuba Hospital, Ibaraki, Japan (T.T., H.N.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tatsuya Oda
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (K.Mi., K.Ma., H.K.); Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan (K.K., T.E., O.S., T.O.); and Tsukuba Human Tissue Biobank Center, University of Tsukuba Hospital, Ibaraki, Japan (T.T., H.N.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroyuki Kusuhara
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (K.Mi., K.Ma., H.K.); Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan (K.K., T.E., O.S., T.O.); and Tsukuba Human Tissue Biobank Center, University of Tsukuba Hospital, Ibaraki, Japan (T.T., H.N.)
  • 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 + SI
  • PDF
Loading

Abstract

Intestinal permeability is a critical factor for orally administered drugs. It can be facilitated by uptake transporters or limited by efflux transporters and metabolic enzymes in the intestine. The present study aimed to characterize the Ussing chamber system incorporating human intestinal tissue as an in vitro model for investigating the impact of intestinal uptake/efflux transporters on the intestinal absorption of substrate drugs in humans. We confirmed the functions of major intestinal uptake/efflux drug transporters in freshly isolated human jejunum sections by demonstrating a significant decrease in the mucosal uptake of cefadroxil (peptide transporter 1) and methotrexate (proton-coupled folate transporter), mucosal-to-serosal permeability of ribavirin (concentrative nucleoside transporters/equilibrative nucleoside transporters), and serosal-to-mucosal permeability of P-glycoprotein and breast cancer resistance protein substrates in the presence of their typical inhibitors. The mucosal-to-serosal apparent permeability coefficients (Papp) of 19 drugs, including substrates of drug transporters and cytochrome P450 3A, ranged from 0.60 × 10−6 to 29 × 10−6 cm/s and showed a good correlation with reported fraction of an oral dose that enters the gut wall and passes into the portal circulation with escaping intestinal metabolism (FaFg) values in humans. Furthermore, the Papp values for cefadroxil, methotrexate, and ribavirin in the presence of the corresponding transporter inhibitors underestimated the FaFg of these drugs, which clearly showed that intestinal uptake transporters facilitate their intestinal absorption in humans. In conclusion, the functions of major intestinal uptake/efflux drug transporters could be maintained in freshly isolated human jejunum sections. The Ussing chamber system incorporating human intestinal tissue would be useful for evaluating the impact of intestinal uptake/efflux transporters on the intestinal absorption of various types of drugs in humans.

SIGNIFICANCE STATEMENT Although previous studies have predicted the intestinal absorption of drugs in humans using the Ussing chamber system incorporating human intestinal tissue, there is little systematic information about drug transport mediated by multiple transporters in this system. We confirmed the functions of major intestinal uptake/efflux transporters in freshly isolated human jejunum sections and demonstrated that the mucosal-to-serosal apparent permeability coefficient of various types of drugs showed a good correlation with reported human FaFg values.

Footnotes

    • Received June 8, 2020.
    • Accepted October 2, 2020.
  • This study was supported by Grant-in-Aid for Scientific Research (B) [Grant 20H03402] (K.Ma. and T.O.) from the Ministry of Education, Culture, Sports, Science, and Technology in Japan.

  • https://doi.org/10.1124/dmd.120.000138.

  • ↵Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • Copyright © 2020 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: 49 (1)
Drug Metabolism and Disposition
Vol. 49, Issue 1
1 Jan 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • 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.
Characterization of the Human Intestinal Drug Transport with Ussing Chamber System Incorporating Freshly Isolated Human Jejunum
(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

Drug Transporter Function in Freshly Isolated Human Jejunum

Kazuyoshi Michiba, Kazuya Maeda, Ko Kurimori, Tsuyoshi Enomoto, Osamu Shimomura, Tomoyo Takeuchi, Hiroyuki Nishiyama, Tatsuya Oda and Hiroyuki Kusuhara
Drug Metabolism and Disposition January 1, 2021, 49 (1) 84-93; DOI: https://doi.org/10.1124/dmd.120.000138

Citation Manager Formats

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

Drug Transporter Function in Freshly Isolated Human Jejunum

Kazuyoshi Michiba, Kazuya Maeda, Ko Kurimori, Tsuyoshi Enomoto, Osamu Shimomura, Tomoyo Takeuchi, Hiroyuki Nishiyama, Tatsuya Oda and Hiroyuki Kusuhara
Drug Metabolism and Disposition January 1, 2021, 49 (1) 84-93; DOI: https://doi.org/10.1124/dmd.120.000138
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • In Vivo Functional Effects of CYP2C9 M1L
  • Clearance pathways: fevipiprant with probenecid perpetrator
  • Predicting Volume of Distribution from In Vitro Parameters
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