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

Pharmacokinetics and Metabolism of a COX-2 Inhibitor, Valdecoxib, in Mice

Ji Y. Zhang, Josh J. Yuan, Yue-Fen Wang, Roy H. Bible Jr. and Alan P. Breau
Drug Metabolism and Disposition April 2003, 31 (4) 491-501; DOI: https://doi.org/10.1124/dmd.31.4.491
Ji Y. Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Josh J. Yuan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yue-Fen Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roy H. Bible Jr.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alan P. Breau
  • 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 pharmacokinetics and metabolism of valdecoxib, a potent cyclooxygenase-2 selective inhibitor, were investigated in mice. Valdecoxib was extensively metabolized after a single 5 mg/kg oral administration of [14C]valdecoxib and elimination of unchanged drug was minor (less than 1%) in male and female mice. The total mean percentage of administered radioactive dose recovered was 99.8% in the male mice and 94.7% in the female mice. Sixteen metabolites were identified in mouse plasma, red blood cells, urine, and feces. The main phase I metabolic pathway of valdecoxib in mice involved the oxidation of the 5-methyl group to form the active hydroxymethyl metabolite M1. M1 was further oxidized to the carboxylic acid metabolite M4, which underwent opening of the isoxazole ring to form M6 and M13. Phase II metabolism included glucuronide, glucoside, and methyl sulfone conjugations. M1 was also conjugated with glucuronic acid and glucose to yield M-G and M1-glucose, respectively. Three novel methylsulfone conjugates M20, M21, and M21-G were detected in blood or urine. Valdecoxib and M1 were the major radioactive components in plasma and red blood cells. The plasma area under the curve from zero to infinity (AUC0-∞) values for valdecoxib and M1 were 3.58 and 0.850 μg · h/ml in males and 2.08 and 1.63 μg · h/ml in females, respectively. The RBC AUC0-∞ values for valdecoxib and M1 were 12.1 and 22.6 μg · h/g in males and 6.42 and 35.2 μg · h/g in females, respectively.

Footnotes

  • Abbreviations used are::
    COX-2
    cyclooxygenase II
    MS
    mass spectrometry
    DPM
    disintegrations per minute
    LOQ
    limit of quantitation
    LSC
    liquid scintillation counting
    RBC
    red blood cells
    HPLC
    high performance liquid chromatography
    HPLRC
    high performance liquid radiochromatography
    LC-MS/MS
    liquid chromatography-tandem mass spectrometry
    CID
    collision induced dissociation
    Q-TOF
    quadrupole-time of flight
    AUC
    area under the curve
    • Received September 30, 2002.
    • Accepted January 6, 2003.
  • 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: 31 (4)
Drug Metabolism and Disposition
Vol. 31, Issue 4
1 Apr 2003
  • 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.
Pharmacokinetics and Metabolism of a COX-2 Inhibitor, Valdecoxib, in Mice
(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

Pharmacokinetics and Metabolism of a COX-2 Inhibitor, Valdecoxib, in Mice

Ji Y. Zhang, Josh J. Yuan, Yue-Fen Wang, Roy H. Bible and Alan P. Breau
Drug Metabolism and Disposition April 1, 2003, 31 (4) 491-501; DOI: https://doi.org/10.1124/dmd.31.4.491

Citation Manager Formats

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

Share
Research ArticleArticle

Pharmacokinetics and Metabolism of a COX-2 Inhibitor, Valdecoxib, in Mice

Ji Y. Zhang, Josh J. Yuan, Yue-Fen Wang, Roy H. Bible and Alan P. Breau
Drug Metabolism and Disposition April 1, 2003, 31 (4) 491-501; DOI: https://doi.org/10.1124/dmd.31.4.491
Reddit logo Twitter logo Facebook 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

  • Cytochrome P450 4F11 in lung cancer
  • SLC49A4-mediated pyrilamine transport
  • Functional Characterization of 29 CYP4F2 Variants
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics