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

Panipenem, A Carbapenem Antibiotic, Enhances the Glucuronidation of Intravenously Administered Valproic Acid in Rats

Naotoshi Yamamura, Kaoru Imura, Hideo Naganuma and Kenji Nishimura
Drug Metabolism and Disposition June 1999, 27 (6) 724-730;
Naotoshi Yamamura
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kaoru Imura
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hideo Naganuma
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenji Nishimura
  • 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

Previously, a significant decrease in the trough plasma-concentration of valproic acid (VPA) owing to the concomitant administration of panipenem (PAPM)/betamipron, a carbapenem antibiotic, in epileptic patients was reported. To determine the site and mechanism of the drug interaction between VPA and PAPM, we performed in vivo and in vitro experiments using rats. A 30 mg/kg bolus dose of VPA was given i.v. to normal Sprague-Dawley rats, nephrectomized rats, and hepatectomized rats, with and without prior treatment of PAPM. PAPM treatment resulted in a significant reduction of biological half-life and a significant increase of total body clearance in normal rats. The effects of PAPM on the disposition kinetics of VPA were also observed in nephrectomized rats, whereas hepatectomy abolished the interaction completely. Thus, the site of interaction was identified as the liver. At steady state, PAPM treatment significantly increased total body clearance, the biliary excretion rate of VPA glucuronide, and the apparent metabolic clearance of VPA by glucuronidation, but did not affect the biliary excretion clearance of VPA glucuronide. Initial uptake velocity of VPA into rat hepatocytes proportionally increased as a function of VPA concentration added and was not affected by PAPM. The plasma-unbound fraction of VPA in vitro was not altered by PAPM. These data demonstrate that PAPM does not affect the uptake of VPA into the liver, the plasma-unbound fraction, and the excretion process of VPA glucuronide. Consequently, PAPM appears to enhance the rate of metabolism of VPA to VPA glucuronide in the liver.

Footnotes

  • Send reprint requests to: Dr. Naotoshi Yamamura, Ph.D., Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd., 2–58, Hiromachi 1-chome Shinagawa-ku, Tokyo 140-8710, Japan. E-mail:yamamu{at}shina.sankyo.co.jp

  • Abbreviations used are::
    VPA
    valproic acid
    VPA-Glu
    valproate glucuronide
    PAPM
    panipenem
    CLtot
    total body clearance
    CLm(glu)
    apparent metabolic clearance of VPA by glucuronidation
    CLbile(glu)
    biliary excretion clearance of VPA-Glu
    Css,plasma(vpa)
    plasma concentration of VPA at steady-state
    Css,liver(glu)
    hepatic concentration of VPA-Glu at steady-state
    Vbile(glu)
    biliary excretion rate of VPA-Glu
    UDPGA
    UDP-glucuronic acid
    SD
    Sprague-Dawley
    14C-VPA
    14C-labeled sodium valproate
    3H-VPA
    3H-labeled sodium valproate
    TLC
    thin-layer chromatography
    • Received September 21, 1998.
    • Accepted February 10, 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 (6)
Drug Metabolism and Disposition
Vol. 27, Issue 6
1 Jun 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.
Panipenem, A Carbapenem Antibiotic, Enhances the Glucuronidation of Intravenously Administered Valproic Acid in Rats
(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

Panipenem, A Carbapenem Antibiotic, Enhances the Glucuronidation of Intravenously Administered Valproic Acid in Rats

Naotoshi Yamamura, Kaoru Imura, Hideo Naganuma and Kenji Nishimura
Drug Metabolism and Disposition June 1, 1999, 27 (6) 724-730;

Citation Manager Formats

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

Share
Research ArticleArticle

Panipenem, A Carbapenem Antibiotic, Enhances the Glucuronidation of Intravenously Administered Valproic Acid in Rats

Naotoshi Yamamura, Kaoru Imura, Hideo Naganuma and Kenji Nishimura
Drug Metabolism and Disposition June 1, 1999, 27 (6) 724-730;
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Improved CYP Reaction Phenotyping
  • Multiple-Concentration Chemical Inhibition Design
  • New Dog P450 3A98 in Gut
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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics