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 Human Corneal Epithelial Cell Model As a Surrogate for Corneal Permeability Assessment: Metabolism and Transport

Cathie D. Xiang, Minerva Batugo, David C. Gale, Tao Zhang, Jingjing Ye, Chunze Li, Sue Zhou, Ellen Y. Wu and Eric Y. Zhang
Drug Metabolism and Disposition May 2009, 37 (5) 992-998; DOI: https://doi.org/10.1124/dmd.108.026286
Cathie D. Xiang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minerva Batugo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David C. Gale
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tao Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jingjing Ye
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chunze Li
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sue Zhou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ellen Y. Wu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric Y. Zhang
  • 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 recently introduced Clonetics human corneal epithelium (cHCE) cell line is considered a promising in vitro permeability model, replacing excised animal cornea to predict corneal permeability of topically administered compounds. The purpose of this study was to further characterize cHCE as a corneal permeability model from both drug metabolism and transport aspects. First, good correlation was found in the permeability values (Papp) obtained from cHCE and rabbit corneas for various ophthalmic drugs and permeability markers. Second, a previously established real-time quantitative polymerase chain reaction method was used to profile mRNA expression of drug-metabolizing enzymes (major cytochromes P450 and UDP glucuronosyltransferase 1A1) and transporters in cHCE in comparison with human cornea. Findings indicated that 1) the mRNA expression of most metabolizing enzymes tested was lower in cHCE than in excised human cornea, 2) the mRNA expression of efflux transporters [multidrug resistant-associated protein (MRP) 1, MRP2, MRP3, and breast cancer resistance protein], peptide transporters (PEPT1 and PEPT2), and organic cation transporters (OCTN1, OCTN2, OCT1, and OCT3) could be detected in cHCE as in human cornea. However, multidrug resistance (MDR) 1 and organic anion transporting polypeptide 2B1 was not detected in cHCE; 3) cHCE was demonstrated to possess both esterase and ketone reductase activities known to be present in human cornea; and 4) transport studies using probe substrates suggested that both active efflux and uptake transport may be limited in cHCE. As the first detailed report to delineate drug metabolism and transport characteristics of cHCE, this work shed light on the usefulness and potential limitations of cHCE in predicting the corneal permeability of ophthalmic drugs, including ester prodrugs, and transporter substrates.

Footnotes

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

  • doi:10.1124/dmd.108.026286.

  • ABBREVIATIONS: HCE, human cornea epithelial; TEER, transepithelial electrical resistance; PCR, polymerase chain reaction; BSS, balanced salt solution; LC, liquid chromatography; MS/MS, tandem mass spectrometry; A, apical; B, basolateral; MRP, multidrug resistant-associated protein; BCRP, breast cancer resistance protein; PEPT, peptide transporter; OCTN, organic cation/carnitine transporter; P-gp, P-glycoprotein; P450, cytochrome P450; UGT, UDP glucuronosyltransferase.

    • Received December 18, 2008.
    • Accepted February 11, 2009.
  • 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: 37 (5)
Drug Metabolism and Disposition
Vol. 37, Issue 5
1 May 2009
  • 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.
Characterization of Human Corneal Epithelial Cell Model As a Surrogate for Corneal Permeability Assessment: Metabolism and Transport
(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 Human Corneal Epithelial Cell Model As a Surrogate for Corneal Permeability Assessment: Metabolism and Transport

Cathie D. Xiang, Minerva Batugo, David C. Gale, Tao Zhang, Jingjing Ye, Chunze Li, Sue Zhou, Ellen Y. Wu and Eric Y. Zhang
Drug Metabolism and Disposition May 1, 2009, 37 (5) 992-998; DOI: https://doi.org/10.1124/dmd.108.026286

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 Human Corneal Epithelial Cell Model As a Surrogate for Corneal Permeability Assessment: Metabolism and Transport

Cathie D. Xiang, Minerva Batugo, David C. Gale, Tao Zhang, Jingjing Ye, Chunze Li, Sue Zhou, Ellen Y. Wu and Eric Y. Zhang
Drug Metabolism and Disposition May 1, 2009, 37 (5) 992-998; DOI: https://doi.org/10.1124/dmd.108.026286
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
  • Mass Balance Recovery and Disposition of AZD4831 in Humans
  • Biotransformation of AZD4831 in Animals and Humans
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