Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • About Us
    • About JPET
    • Feedback
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • 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

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • About Us
    • About JPET
    • Feedback
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleMetabolism, Transport, and Pharmacogenomics

Potential Drug Interactions Mediated by Renal Organic Anion Transporter OATP4C1

Toshihiro Sato, Eikan Mishima, Nariyasu Mano, Takaaki Abe and Hiroaki Yamaguchi
Journal of Pharmacology and Experimental Therapeutics August 2017, 362 (2) 271-277; DOI: https://doi.org/10.1124/jpet.117.241703
Toshihiro Sato
Department of Pharmaceutical Sciences, Tohoku University Hospital (T.S., N.M., H.Y.); Division of Nephrology, Endocrinology, and Vascular Medicine, Graduate School of Medicine (E.M., T.A.); Division of Medical Science, Graduate School of Biomedical Engineering (T.A.); Department of Clinical Biology and Hormonal Regulation, Graduate School of Medicine (T.A.), Tohoku University, Sendai, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eikan Mishima
Department of Pharmaceutical Sciences, Tohoku University Hospital (T.S., N.M., H.Y.); Division of Nephrology, Endocrinology, and Vascular Medicine, Graduate School of Medicine (E.M., T.A.); Division of Medical Science, Graduate School of Biomedical Engineering (T.A.); Department of Clinical Biology and Hormonal Regulation, Graduate School of Medicine (T.A.), Tohoku University, Sendai, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nariyasu Mano
Department of Pharmaceutical Sciences, Tohoku University Hospital (T.S., N.M., H.Y.); Division of Nephrology, Endocrinology, and Vascular Medicine, Graduate School of Medicine (E.M., T.A.); Division of Medical Science, Graduate School of Biomedical Engineering (T.A.); Department of Clinical Biology and Hormonal Regulation, Graduate School of Medicine (T.A.), Tohoku University, Sendai, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takaaki Abe
Department of Pharmaceutical Sciences, Tohoku University Hospital (T.S., N.M., H.Y.); Division of Nephrology, Endocrinology, and Vascular Medicine, Graduate School of Medicine (E.M., T.A.); Division of Medical Science, Graduate School of Biomedical Engineering (T.A.); Department of Clinical Biology and Hormonal Regulation, Graduate School of Medicine (T.A.), Tohoku University, Sendai, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroaki Yamaguchi
Department of Pharmaceutical Sciences, Tohoku University Hospital (T.S., N.M., H.Y.); Division of Nephrology, Endocrinology, and Vascular Medicine, Graduate School of Medicine (E.M., T.A.); Division of Medical Science, Graduate School of Biomedical Engineering (T.A.); Department of Clinical Biology and Hormonal Regulation, Graduate School of Medicine (T.A.), Tohoku University, Sendai, 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

Organic anion-transporting polypeptide 4C1 (OATP4C1) is an organic anion transporter expressed in the basolateral membrane of the renal proximal tubules. It plays a major role in the urinary excretion of both exogenous drugs and endogenous compounds. Our previous studies have indicated the importance of OATP4C1 in pathologic and physiologic conditions; however, the majority of its pharmacologic characteristics remained unclear. Therefore, to provide essential information for clinical drug therapy decisions and drug development, we clarified drug interactions mediated by OATP4C1. To elucidate potential drug interactions via OATP4C1, we screened 53 representative drugs commonly used in clinical settings. Next, we evaluated the IC50 values of drugs that inhibited OATP4C1 by more than 50%. To apply our results to clinical settings, we calculated the drug-drug interaction (DDI) indices. The screening analysis using an OATP4C1-expressing cell system demonstrated that 22 out of 53 therapeutic drugs inhibited OATP4C1-mediated triiodothyronine transport. In particular, OATP4C1-mediated transport was strongly inhibited by 10 drugs. The IC50 values of 10 drugs—nicardipine, spironolactone, fluvastatin, crizotinib, levofloxacin, clarithromycin, ritonavir, saquinavir, quinidine, and verapamil—obtained in this study were 51, 53, 41, 24, 420, 200, 8.5, 4.3, 100, and 110 µM, respectively. The IC50 values of these drugs were higher than the plasma concentrations obtained in clinical practice. However, ritonavir showed the highest DDI index (1.9) for OATP4C1, suggesting that it may strongly influence this transporter and thus cause drug interactions seen in clinical settings. Our finding gives new insight into the role of OATP4C1 in clinical DDIs.

Footnotes

    • Received March 27, 2017.
    • Accepted May 24, 2017.
  • This work was supported by grants from the Japan Society for the Promotion of Science KAKENHI [Grant 23790168 (to H.Y.) and 15H00485 (to T.S.)].

  • https://doi.org/10.1124/jpet.117.241703.

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

  • Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

Log in using your username and password

Forgot your user name or password?

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 362 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 362, Issue 2
1 Aug 2017
  • 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 Journal of Pharmacology and Experimental Therapeutics 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.
Potential Drug Interactions Mediated by Renal Organic Anion Transporter OATP4C1
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
Citation Tools
Research ArticleMetabolism, Transport, and Pharmacogenomics

Potential Drug Interactions via OATP4C1

Toshihiro Sato, Eikan Mishima, Nariyasu Mano, Takaaki Abe and Hiroaki Yamaguchi
Journal of Pharmacology and Experimental Therapeutics August 1, 2017, 362 (2) 271-277; DOI: https://doi.org/10.1124/jpet.117.241703

Citation Manager Formats

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

Share
Research ArticleMetabolism, Transport, and Pharmacogenomics

Potential Drug Interactions via OATP4C1

Toshihiro Sato, Eikan Mishima, Nariyasu Mano, Takaaki Abe and Hiroaki Yamaguchi
Journal of Pharmacology and Experimental Therapeutics August 1, 2017, 362 (2) 271-277; DOI: https://doi.org/10.1124/jpet.117.241703
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
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Hepatobiliary disposition of atovaquone: A case of mechanistically unusual biliary clearance
  • In vitro – in vivo extrapolation of OATP1B-mediated drug-drug interactions in cynomolgus monkey
  • FXR Agonists Increase Bile Acid Efflux in Human Hepatocytes
Show more Metabolism, Transport, and Pharmacogenomics

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 JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2018 by the American Society for Pharmacology and Experimental Therapeutics