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
OtherArticle

Simultaneous evaluation of membrane permeability and UDP-glucuronosyltransferase-mediated metabolism of food-derived compounds using human induced pluripotent stem cell-derived small intestinal epithelial cells

Takashi Kitaguchi, Taisei Mizota, Mina Ito, Katsutoshi Ohno, Kazuhiro Kobayashi, Isamu Ogawa, Shimeng Qiu, Takahiro Iwao, Nobumitsu Hanioka, Mitsuru Tanaka and Tamihide Matsunaga
Drug Metabolism and Disposition October 20, 2021, DMD-AR-2021-000605; DOI: https://doi.org/10.1124/dmd.121.000605
Takashi Kitaguchi
1Global Food Safety Institute, Nissin Foods Holdings Co., Ltd., Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: takashi.kitaguchi@nissin.com
Taisei Mizota
1Global Food Safety Institute, Nissin Foods Holdings Co., Ltd., Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mina Ito
1Global Food Safety Institute, Nissin Foods Holdings Co., Ltd., Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katsutoshi Ohno
1Global Food Safety Institute, Nissin Foods Holdings Co., Ltd., Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuhiro Kobayashi
1Global Food Safety Institute, Nissin Foods Holdings Co., Ltd., Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Isamu Ogawa
2Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shimeng Qiu
2Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takahiro Iwao
3Nagoya City University, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nobumitsu Hanioka
4Department of Health Pharmacy, Yokohama University of Pharmacy, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mitsuru Tanaka
1Global Food Safety Institute, Nissin Foods Holdings Co., Ltd., Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tamihide Matsunaga
2Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan
  • 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

Pharmacokinetic prediction after oral ingestion is important for quantitative risk assessment of food-derived compounds. To evaluate the utility of human intestinal absorption prediction, we compared the membrane permeability and metabolic activities of human induced pluripotent stem cell-derived small intestinal epithelial cells (hiPSC-SIECs) with Caco-2 cells or human primary enterocytes (hPECs). We found that membrane permeability in hiPSC-SIECs had better predictivity than that in Caco-2 cells against 21 drugs with known human intestinal availability (r = 0.830 and 0.401, respectively). Membrane permeability in hiPSC-SIECs was only 0.019-0.25-fold as compared with that in Caco-2 cells for 7 in 15 food-derived compounds, primarily those which were reported to undergo glucuronidation metabolism. The metabolic rates of the glucuronide conjugate were similar or higher in hiPSC-SIECs as compared with hPECs, while lower in Caco-2 cells. Expression levels of UDP-glucuronosyltransferase (UGT) isoform mRNA in hiPSC-SIECs were similar or higher as compared with hPECs. Therefore, hiPSC-SIECs could be a useful tool for predicting human intestinal absorption, in order to simultaneously evaluate membrane permeability and UGT-mediated metabolism.

Significance Statement Gastrointestinal absorption is an important step for predicting the internal exposure of food-derived compounds. This research revealed that human induced pluripotent stem cell-derived small intestinal cells (hiPSC-SIECs) had better predictivity of intestinal availability than Caco-2 cells; furthermore, the metabolic rates of UGT substrates of hiPSC-SIECs were closer those of human primary enterocytes than those of Caco-2 cells. Therefore, hiPSC-SIECs could be a useful tool for predicting human intestinal absorption to simultaneously evaluate membrane permeability and UGT-mediated metabolism.

  • Caco-2 cell
  • first-pass metabolism
  • glucuronidation/UDP-glucuronyltransferases/UGT
  • intestinal bioavailability
  • oral absorption
  • stem cells
  • Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics
Next
Back to top

In this issue

Drug Metabolism and Disposition: 51 (2)
Drug Metabolism and Disposition
Vol. 51, Issue 2
1 Feb 2023
  • 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.
Simultaneous evaluation of membrane permeability and UDP-glucuronosyltransferase-mediated metabolism of food-derived compounds using human induced pluripotent stem cell-derived small intestinal epithelial cells
(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
OtherArticle

Membrane permeability and UGT metabolism in hiPSC-SIECs

Takashi Kitaguchi, Taisei Mizota, Mina Ito, Katsutoshi Ohno, Kazuhiro Kobayashi, Isamu Ogawa, Shimeng Qiu, Takahiro Iwao, Nobumitsu Hanioka, Mitsuru Tanaka and Tamihide Matsunaga
Drug Metabolism and Disposition October 20, 2021, DMD-AR-2021-000605; DOI: https://doi.org/10.1124/dmd.121.000605

Citation Manager Formats

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

Share
OtherArticle

Membrane permeability and UGT metabolism in hiPSC-SIECs

Takashi Kitaguchi, Taisei Mizota, Mina Ito, Katsutoshi Ohno, Kazuhiro Kobayashi, Isamu Ogawa, Shimeng Qiu, Takahiro Iwao, Nobumitsu Hanioka, Mitsuru Tanaka and Tamihide Matsunaga
Drug Metabolism and Disposition October 20, 2021, DMD-AR-2021-000605; DOI: https://doi.org/10.1124/dmd.121.000605
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
  • Biotransformation of Trastuzumab and Pertuzumab
Show more Article

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