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

IN VITRO METABOLISM OF FERROQUINE (SSR97193) IN ANIMAL AND HUMAN HEPATIC MODELS AND ANTIMALARIAL ACTIVITY OF MAJOR METABOLITES ON PLASMODIUM FALCIPARUM

Wassim Daher, Lydie Pelinski, Sylvie Klieber, Freddy Sadoun, Viviane Meunier, Martine Bourrié, Christophe Biot, François Guillou, Gérard Fabre, Jacques Brocard, Laurent Fraisse, Jean-Pierre Maffrand, Jamal Khalife and Daniel Dive
Drug Metabolism and Disposition April 2006, 34 (4) 667-682; DOI: https://doi.org/10.1124/dmd.104.003202
Wassim Daher
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lydie Pelinski
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sylvie Klieber
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Freddy Sadoun
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Viviane Meunier
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martine Bourrié
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christophe Biot
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
François Guillou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gérard Fabre
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacques Brocard
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laurent Fraisse
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Pierre Maffrand
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jamal Khalife
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel Dive
  • 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

Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.

Footnotes

  • This work and W.D. were supported by Sanofi Aventis.

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

  • doi:10.1124/dmd.104.003202.

  • ABBREVIATIONS: P450, cytochrome P450; HPLC-UV, high-performance liquid chromatography coupled with UV detection; TOF-MS/MS, quadrupole time-of-flight/tandem mass spectrometry; FMO, flavin-containing mono-oxygenase; Q-TOF, quadrupole-time of flight; DMFQ, mono-N-demethyl-ferroquine; HPLC-MS/MS, high-performance liquid chromatography/tandem mass spectrometry; DMSO, dimethyl sulfoxide; FQ, ferroquine; DMFQ, mono-N-demethyl ferroquine; HH, human hepatocyte metabolite.

    • Received December 2, 2004.
    • Accepted January 12, 2006.
  • 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: 34 (4)
Drug Metabolism and Disposition
Vol. 34, Issue 4
1 Apr 2006
  • 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.
IN VITRO METABOLISM OF FERROQUINE (SSR97193) IN ANIMAL AND HUMAN HEPATIC MODELS AND ANTIMALARIAL ACTIVITY OF MAJOR METABOLITES ON PLASMODIUM FALCIPARUM
(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

IN VITRO METABOLISM OF FERROQUINE (SSR97193) IN ANIMAL AND HUMAN HEPATIC MODELS AND ANTIMALARIAL ACTIVITY OF MAJOR METABOLITES ON PLASMODIUM FALCIPARUM

Wassim Daher, Lydie Pelinski, Sylvie Klieber, Freddy Sadoun, Viviane Meunier, Martine Bourrié, Christophe Biot, François Guillou, Gérard Fabre, Jacques Brocard, Laurent Fraisse, Jean-Pierre Maffrand, Jamal Khalife and Daniel Dive
Drug Metabolism and Disposition April 1, 2006, 34 (4) 667-682; DOI: https://doi.org/10.1124/dmd.104.003202

Citation Manager Formats

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

Share
Research ArticleArticle

IN VITRO METABOLISM OF FERROQUINE (SSR97193) IN ANIMAL AND HUMAN HEPATIC MODELS AND ANTIMALARIAL ACTIVITY OF MAJOR METABOLITES ON PLASMODIUM FALCIPARUM

Wassim Daher, Lydie Pelinski, Sylvie Klieber, Freddy Sadoun, Viviane Meunier, Martine Bourrié, Christophe Biot, François Guillou, Gérard Fabre, Jacques Brocard, Laurent Fraisse, Jean-Pierre Maffrand, Jamal Khalife and Daniel Dive
Drug Metabolism and Disposition April 1, 2006, 34 (4) 667-682; DOI: https://doi.org/10.1124/dmd.104.003202
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
    • Conclusion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • A PBPK model for CBD in adults and children
  • Mass Balance Recovery and Disposition of AZD4831 in Humans
  • Biotransformation of AZD4831 in Animals and Humans
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