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

Apixaban Metabolism and Pharmacokinetics after Oral Administration to Humans

Nirmala Raghavan, Charles E. Frost, Zhigang Yu, Kan He, Haiying Zhang, W. Griffith Humphreys, Donald Pinto, Shiangyuan Chen, Samuel Bonacorsi, Pancras C. Wong and Donglu Zhang
Drug Metabolism and Disposition January 2009, 37 (1) 74-81; DOI: https://doi.org/10.1124/dmd.108.023143
Nirmala Raghavan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Charles E. Frost
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhigang Yu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kan He
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haiying Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
W. Griffith Humphreys
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Donald Pinto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shiangyuan Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Samuel Bonacorsi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pancras C. Wong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Donglu Zhang
  • 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 and disposition of [14C]apixaban, an orally bioavailable, highly selective, and direct acting/reversible factor Xa inhibitor, was investigated in 10 healthy male subjects without (group 1, n = 6) and with bile collection (group 2, n = 4) after a single 20-mg oral dose. Urine, blood, and feces samples were collected from all subjects. Bile samples were also collected for 3 to 8 h after dosing from group 2 subjects. There were no serious adverse events or discontinuations due to adverse effects. In plasma, apixaban was the major circulating component and O-demethyl apixaban sulfate, a stable and water-soluble metabolite, was the significant metabolite. The exposure of apixaban (Cmax and area under the plasma concentration versus time curve) in subjects with bile collection was generally similar to that in subjects without bile collection. The administered dose was recovered in feces (group 1, 56.0%; group 2, 46.7%) and urine (group 1, 24.5%; group 2, 28.8%), with the parent drug representing approximately half of the recovered dose. Biliary excretion represented a minor elimination pathway (2.44% of the administered dose) from group 2 subjects within the limited collection period. Metabolic pathways identified for apixaban included O-demethylation, hydroxylation, and sulfation of hydroxylated O-demethyl apixaban. Thus, apixaban is an orally bioavailable inhibitor of factor Xa with elimination pathways that include metabolism and renal excretion.

Footnotes

  • This study was funded by Bristol-Myers Squibb and Pfizer.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.108.023143.

  • ABBREVIATIONS: PK, pharmacokinetics; BMS-562247, 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5-dihydro pyrazolo[5,4-c]pyridine-3-carboxamide; HPLC, high-pressure liquid chromatography; HRMS, high-resolution mass spectrometry; TRA, total radioactivity; Q-TOF, quadrupole time of flight; MS, mass spectrometry; LC, liquid chromatography; MS/MS, tandem mass spectrometry; AUC, area under the plasma concentration versus time curve; LLOQ, lower limit of quantitation; AE, adverse event.

    • Received June 26, 2008.
    • Accepted October 1, 2008.
  • 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: 37 (1)
Drug Metabolism and Disposition
Vol. 37, Issue 1
1 Jan 2009
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • 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 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.
Apixaban Metabolism and Pharmacokinetics after Oral Administration to Humans
(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

Apixaban Metabolism and Pharmacokinetics after Oral Administration to Humans

Nirmala Raghavan, Charles E. Frost, Zhigang Yu, Kan He, Haiying Zhang, W. Griffith Humphreys, Donald Pinto, Shiangyuan Chen, Samuel Bonacorsi, Pancras C. Wong and Donglu Zhang
Drug Metabolism and Disposition January 1, 2009, 37 (1) 74-81; DOI: https://doi.org/10.1124/dmd.108.023143

Citation Manager Formats

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

Share
Research ArticleArticle

Apixaban Metabolism and Pharmacokinetics after Oral Administration to Humans

Nirmala Raghavan, Charles E. Frost, Zhigang Yu, Kan He, Haiying Zhang, W. Griffith Humphreys, Donald Pinto, Shiangyuan Chen, Samuel Bonacorsi, Pancras C. Wong and Donglu Zhang
Drug Metabolism and Disposition January 1, 2009, 37 (1) 74-81; DOI: https://doi.org/10.1124/dmd.108.023143
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
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Warfarin PBPK Model with TMDD Mechanism
  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
Show more Articles

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