Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Metabolism and Disposition of the Metabotropic Glutamate Receptor 5 Antagonist (mGluR5) Mavoglurant (AFQ056) in Healthy Subjects

Markus Walles, Thierry Wolf, Yi Jin, Michael Ritzau, Luc Alexis Leuthold, Joel Krauser, Hans-Peter Gschwind, David Carcache, Matthias Kittelmann, Magdalena Ocwieja, Mike Ufer, Ralph Woessner, Abhijit Chakraborty and Piet Swart
Drug Metabolism and Disposition September 2013, 41 (9) 1626-1641; DOI: https://doi.org/10.1124/dmd.112.050716
Markus Walles
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thierry Wolf
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yi Jin
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Ritzau
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luc Alexis Leuthold
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joel Krauser
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hans-Peter Gschwind
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Carcache
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthias Kittelmann
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Magdalena Ocwieja
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mike Ufer
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ralph Woessner
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abhijit Chakraborty
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Piet Swart
Drug Metabolism and Pharmacokinetics (M.W., T.W., Y.J., L.A.L., J.K., H.-P.G, R.W., A.C., P.S.), Analytical Sciences (M.R.), Global Discovery Chemistry (M.K., D.C.), Clinical Science & Innovation (M.O.), and Translational Medicine (M.U.), Novartis Institutes for Biomedical Research, Basel, Switzerland
  • 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 disposition and biotransformation of 14C-radiolabeled mavoglurant were investigated in four healthy male subjects after a single oral dose of 200 mg. Blood, plasma, urine, and feces collected over 7 days were analyzed for total radioactivity, mavoglurant was quantified in plasma by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), and metabolite profiles were generated in plasma and excreta by high-performance liquid chromatography (HPLC) and radioactivity detection. The chemical structures of mavoglurant metabolites were characterized by LC-MS/MS, wet-chemical and enzymatic methods, NMR spectroscopy, and comparison with reference compounds. Mavoglurant was safe and well tolerated in this study population. Mavoglurant absorption was ≥50% of dose reaching mean plasma Cmax values of 140 ng/ml (mavoglurant) and 855 ng-eq/ml (total radioactivity) at 2.5 and 3.6 hours, respectively. Thereafter, mavoglurant and total radioactivity concentrations declined with mean apparent half-lives of 12 and 18 hours, respectively. The elimination of mavoglurant occurred predominantly by oxidative metabolism involving primarily 1) oxidation of the tolyl-methyl group to a benzyl-alcohol metabolite (M7) and subsequently to a benzoic acid metabolite (M6), and 2) oxidation of the phenyl-ring leading to a hydroxylated metabolite (M3). The subjects were mainly exposed to mavoglurant and seven main metabolites, which combined accounted for 60% of 14C-AUC0–72 h (area under the concentration-time curve from time 0 to infinity). The primary steps of mavoglurant metabolism observed in vivo could partially be reproduced in vitro in incubations with human liver microsomes and recombinant cytochrome P450 enzymes. After 7 days, the mean balance of total radioactivity excretion was almost complete (95.3% of dose) with 36.7% recovered in urine and 58.6% in feces.

Footnotes

    • Received January 24, 2013.
    • Accepted June 13, 2013.
  • This work was supported by Novartis Pharma AG.

  • dx.doi.org/10.1124/dmd.112.050716.

  • Copyright © 2013 by 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: 41 (9)
Drug Metabolism and Disposition
Vol. 41, Issue 9
1 Sep 2013
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • 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.
Metabolism and Disposition of the Metabotropic Glutamate Receptor 5 Antagonist (mGluR5) Mavoglurant (AFQ056) in Healthy Subjects
(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

Mavoglurant: Human ADME

Markus Walles, Thierry Wolf, Yi Jin, Michael Ritzau, Luc Alexis Leuthold, Joel Krauser, Hans-Peter Gschwind, David Carcache, Matthias Kittelmann, Magdalena Ocwieja, Mike Ufer, Ralph Woessner, Abhijit Chakraborty and Piet Swart
Drug Metabolism and Disposition September 1, 2013, 41 (9) 1626-1641; DOI: https://doi.org/10.1124/dmd.112.050716

Citation Manager Formats

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

Mavoglurant: Human ADME

Markus Walles, Thierry Wolf, Yi Jin, Michael Ritzau, Luc Alexis Leuthold, Joel Krauser, Hans-Peter Gschwind, David Carcache, Matthias Kittelmann, Magdalena Ocwieja, Mike Ufer, Ralph Woessner, Abhijit Chakraborty and Piet Swart
Drug Metabolism and Disposition September 1, 2013, 41 (9) 1626-1641; DOI: https://doi.org/10.1124/dmd.112.050716
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Humanized PXR-CAR-CYP3A4/7 Mouse as Model of Induction
  • Ozanimod Human Metabolism and Disposition
  • Clearance Pathways: Fevipiprant with Probenecid Perpetrator
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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics