Skip to main content
Advertisement

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
  • 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

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
Drug Metabolism & Disposition

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
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Retigabine N-Glucuronidation and Its Potential Role in Enterohepatic Circulation

Anita Hiller, Nghia Nguyen, Christian P. Strassburg, Qing Li, Harald Jainta, Birgit Pechstein, Peter Ruus, Jürgen Engel, Robert H. Tukey and Thomas Kronbach
Drug Metabolism and Disposition May 1999, 27 (5) 605-612;
Anita Hiller
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nghia Nguyen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christian P. Strassburg
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Qing Li
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Harald Jainta
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Birgit Pechstein
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Ruus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jürgen Engel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert H. Tukey
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Kronbach
  • 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 metabolism of retigabine in humans and dogs is dominated byN-glucuronidation (McNeilly et al., 1997), whereas in rats, a multitude of metabolites of this new anticonvulsant is observed (Hempel et al., 1999). The comparison of the in vivo and in vitro kinetics of retigabine N-glucuronidation in these species identified a constant ratio between retigabine and retigabineN-glucuronide in vivo in humans and dog. An enterohepatic circulation of retigabine in these species is likely to be the result of reversible glucuronidation-deglucuronidation reactions. Rats did not show such a phenomenon, indicating that enterohepatic circulation of retigabine via retigabineN-glucuronide does not occur in this species. In the rat, 90% of retigabine N-glucuronidation is catalyzed by UDP-glucuronosyltransferase (UGT)1A1 and UGT1A2, whereas family 2 UGT enzymes contribute also. Of ten recombinant human UGTs, only UGTs 1A1, 1A3, 1A4, and 1A9 catalyzed theN-glucuronidation of retigabine. From the known substrate specificities of UGT1A4 toward lamotrigine and bilirubin and our activity and inhibition data, we conclude that UGT1A4 is a major retigabine N-glucuronosyl transferase in vivo and significantly contributes to the enterohepatic cycling of the drug.

Footnotes

  • Send reprint requests to: Dr. Thomas Kronbach, Corporate Research & Development ASTA Medica Group, Biochemistry Dresden, Arzneimittelwerk Dresden GmbH, Meiβner Str. 191, D-01445 Radebeul, Germany. E-mail: Dr_Thomas.Kronbach{at}astamedica.de

  • This work was supported in part by grants from the Sächsisches Ministerium für Arbeit und Wirtschaft (project number 1791) and by United States Public Health Service Grant GM49135 (R.H.T).

  • Abbreviations used are::
    UGT
    UDP-glucuronosyltransferase
    AUC
    area under the plasma concentration-time curve from t0 up to t∞
    HPLC
    high-performance liquid chromatography
    EHC
    enterohepatic circulation
    UDPGA
    UDP-glucuronic acid
    • Received July 22, 1998.
    • Accepted January 25, 1999.
  • 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

Drug Metabolism and Disposition: 27 (5)
Drug Metabolism and Disposition
Vol. 27, Issue 5
1 May 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.
Retigabine N-Glucuronidation and Its Potential Role in Enterohepatic Circulation
(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.
Citation Tools
Research ArticleArticle

Retigabine N-Glucuronidation and Its Potential Role in Enterohepatic Circulation

Anita Hiller, Nghia Nguyen, Christian P. Strassburg, Qing Li, Harald Jainta, Birgit Pechstein, Peter Ruus, Jürgen Engel, Robert H. Tukey and Thomas Kronbach
Drug Metabolism and Disposition May 1, 1999, 27 (5) 605-612;

Citation Manager Formats

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

Retigabine N-Glucuronidation and Its Potential Role in Enterohepatic Circulation

Anita Hiller, Nghia Nguyen, Christian P. Strassburg, Qing Li, Harald Jainta, Birgit Pechstein, Peter Ruus, Jürgen Engel, Robert H. Tukey and Thomas Kronbach
Drug Metabolism and Disposition May 1, 1999, 27 (5) 605-612;
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

  • P450 Activities in Paired Liver and Small Intestinal Samples
  • Numerical Analysis of Time-Dependent Inhibition by MDMA
  • NRF2-Independent Regulation of DMEs by Cadmium and ITCs
Show more Article

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 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 © 2019 by the American Society for Pharmacology and Experimental Therapeutics