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
  • Log out
  • My Cart

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
  • Log out
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
OtherDRUG METABOLISM AND DISPOSITION

Carrier-Mediated Hepatic Uptake of Quinolone Antibiotics in the Rat

Hiroyuki Sasabe, Tetsuya Terasaki, Akira Tsuji and Yuichi Sugiyama
Journal of Pharmacology and Experimental Therapeutics July 1997, 282 (1) 162-171;
Hiroyuki Sasabe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tetsuya Terasaki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Akira Tsuji
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuichi Sugiyama
  • 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 systemic clearance of many quinolone antibiotics is mainly via metabolism and urinary excretion; by contrast, biliary excretion is a major route of elimination for a new quinolone grepafloxacin (GPFX). Accordingly, we studied the hepatic uptake of GPFX because it is the first step in the drug’s hepatobiliary transport. The hepatic uptake of GPFX in vivo after i.v. administration was found to approach the hepatic blood flow, suggesting the existence of an effective hepatic uptake mechanism. To clarify this transport mechanism, GPFX uptake by isolated rat hepatocytes was examined and found to consist of a saturable component (Km 173 μM, Vmax 6.96 nmol/min/mg) and a nonspecific diffusion component. The inhibition of GPFX uptake by ATP-depletors and a lack of effect after replacing Na+ with choline demonstrated that the uptake was an Na+-independent carrier-mediated active process. This uptake was inhibited by other quinolones and for lomefloxacin this was competitive in nature. Mutual inhibition studies were undertaken to investigate whether the transporter for GPFX might be the same as other transporters so far identified. GPFX inhibited the uptake of taurocholic acid, pravastatin (organic anion), cimetidine (organic cation) and ouabain (neutral steroid). However, GPFX uptake was not inhibited by these compounds. Confirmation that GPFX uptake is blood flow limited was obtained by extrapolation of the in vitro data based on mathematical modeling. In conclusion, the effective hepatic uptake of quinolone antibiotics are via carrier-mediated active transport, which is distinct from that involved in the transport of bile acids, organic anions, organic cations or neutral steroids.

Footnotes

  • Send reprint requests to: Dr. Yuichi Sugiyama, Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113, Japan.

  • Abbreviations:
    NQ
    quinolone antibiotics
    GPFX
    grepafloxacin
    SPFX
    sparfloxacin
    LFLX
    lomefloxacin
    OFLX
    ofloxacin
    CPFX
    ciprofloxacin
    ENX
    enoxacin
    TCA
    taurocholic acid
    oatp
    organic anion transporting polypeptide
    FCCP
    carbonylcyanide-p(trifluoromethoxy)phenyl-hydrazone
    DBSP
    dibromosulfophthalein
    DIDS
    4,4′-diisothiocyanatostilbene 2,2′-disulfonic acid
    PCMB
    p-chloromercuribenzoic acid
    ICG
    indocyanine green
    PAEB
    procainamide ethobromide
    TEA
    triethylmethylammonium
    HEPES
    4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid
    Km
    Michaelis-Menten constant, Vmax, maximum uptake rate
    Pdif
    nonspecific uptake clearance
    CL
    clearance
    AUC
    area under the curve
    Qh
    hepatic blood flow
    TLC
    thin-layer chromatography
    HPLC
    high performance liquid chromatography
    oatp
    organic anion transporting polypeptide
    • Received September 5, 1996.
    • Accepted March 21, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 1
1 Jul 1997
  • Table of Contents
  • Index by author
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.
Carrier-Mediated Hepatic Uptake of Quinolone Antibiotics in the Rat
(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.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherDRUG METABOLISM AND DISPOSITION

Carrier-Mediated Hepatic Uptake of Quinolone Antibiotics in the Rat

Hiroyuki Sasabe, Tetsuya Terasaki, Akira Tsuji and Yuichi Sugiyama
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 162-171;

Citation Manager Formats

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

Share
OtherDRUG METABOLISM AND DISPOSITION

Carrier-Mediated Hepatic Uptake of Quinolone Antibiotics in the Rat

Hiroyuki Sasabe, Tetsuya Terasaki, Akira Tsuji and Yuichi Sugiyama
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 162-171;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Methods and Materials
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • A New Interpretation of Salicylic Acid Transport across the Lipid Bilayer: Implications of pH-Dependent but not Carrier-Mediated Absorption from the Gastrointestinal Tract
  • Characterization of Efflux Transport of Organic Anions in a Mouse Brain Capillary Endothelial Cell Line
  • Activation of Human Liver 3α-Hydroxysteroid Dehydrogenase by Clofibrate Derivatives
Show more DRUG METABOLISM AND DISPOSITION

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 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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics