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

OATP and P-Glycoprotein Transporters Mediate the Cellular Uptake and Excretion of Fexofenadine

Mirjana Cvetkovic, Brenda Leake, Martin F. Fromm, Grant R. Wilkinson and Richard B. Kim
Drug Metabolism and Disposition August 1999, 27 (8) 866-871;
Mirjana Cvetkovic
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brenda Leake
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin F. Fromm
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Grant R. Wilkinson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard B. Kim
  • 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

Fexofenadine, a nonsedating antihistamine, does not undergo significant metabolic biotransformation. Accordingly, it was hypothesized that uptake and efflux transporters could be importantly involved in the drug’s disposition. Utilizing a recombinant vaccinia expression system, members of the organic anion transporting polypeptide family, such as the human organic anion transporting polypeptide (OATP) and rat organic anion transporting polypeptides 1 and 2 (Oatp1 and Oatp2), were found to mediate [14C]fexofenadine cellular uptake. On the other hand, the bile acid transporter human sodium taurocholate cotransporting polypeptide (NTCP) and the rat organic cation transporter rOCT1 did not exhibit such activity. P-glycoprotein (P-gp) was identified as a fexofenadine efflux transporter, using the LLC-PK1 cell, a polarized epithelial cell line lacking P-gp, and the derivative cell line (L-MDR1), which overexpresses P-gp. In addition, oral and i.v. administration of [14C]fexofenadine to mice lackingmdr1a-encoded P-gp resulted in 5- and 9-fold increases in the drug’s plasma and brain levels, respectively, compared with wild-type mice. Also, a number of drug inhibitors of P-gp were found to be effective inhibitors of OATP. Because OATP transporters and P-gp colocalize in organs of importance to drug disposition such as the liver, their activity provides an explanation for the heretofore unknown mechanism(s) responsible for fexofenadine’s disposition and suggests potentially similar roles in the disposition of other xenobiotics.

Footnotes

  • Send reprint requests to: Dr. Richard B. Kim, 572 MRB1, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-6602. E-mail:richard.kim{at}mcmail.vanderbilt.edu

  • This work was supported in part by U.S. Public Health Service Grants GM54724, GM31304, and GM07569, and the Deutsche Forschungsgemeinschaft (M.F.F.).

  • Abbreviations used are::
    OATP
    human organic anion transporting polypeptide
    MDR
    multidrug resistance
    P-gp
    P-glycoprotein
    Oatp1
    rat organic anion transporting polypeptide 1
    Oatp2
    rat organic anion transporting polypeptide 2
    NTCP
    human sodium taurocholate cotransporting polypeptide
    rOCT1
    rat organic cation transporter 1
    PCR
    polymerase chain reaction
    • Received February 4, 1999.
    • Accepted May 3, 1999.
  • 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: 27 (8)
Drug Metabolism and Disposition
Vol. 27, Issue 8
1 Aug 1999
  • 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.
OATP and P-Glycoprotein Transporters Mediate the Cellular Uptake and Excretion of Fexofenadine
(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

OATP and P-Glycoprotein Transporters Mediate the Cellular Uptake and Excretion of Fexofenadine

Mirjana Cvetkovic, Brenda Leake, Martin F. Fromm, Grant R. Wilkinson and Richard B. Kim
Drug Metabolism and Disposition August 1, 1999, 27 (8) 866-871;

Citation Manager Formats

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

OATP and P-Glycoprotein Transporters Mediate the Cellular Uptake and Excretion of Fexofenadine

Mirjana Cvetkovic, Brenda Leake, Martin F. Fromm, Grant R. Wilkinson and Richard B. Kim
Drug Metabolism and Disposition August 1, 1999, 27 (8) 866-871;
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
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • High-Throughput Characterization of SLCO1B1 VUS
  • Clearance Pathways: Fevipiprant with Probenecid Perpetrator
  • Retroconversion of PQ and Its N-Oxide Metabolites
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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics