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

Cytochrome P4503A4-Mediated N-Demethylation of the Antiprogestins Lilopristone and Onapristone

Graham R. Jang and Leslie Z. Benet
Drug Metabolism and Disposition October 1997, 25 (10) 1119-1122;
Graham R. Jang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leslie Z. Benet
  • 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 of two newer antiprogestational agents, lilopristone and onapristone, was investigated using human liver microsomes, and evidence was obtained supporting a principal role of cytochrome P450 (CYP) 3A4 in their N-demethylations. Kinetic studies with microsomes from three organ donors indicated lack of biphasic kinetics at substrate concentrations up to 200 μM, consistent with a single enzyme mediating the oxidations. Selective chemical inhibitors of CYP1A2 (furafylline), CYP2C9 (sulfaphenazole), CYP2D6 (quinidine), and CYP2A6/2E1 (diethyldithiocarbamic acid) did not affect initial rates of metabolism of either steroid. Gestodene and triacetyloleandomycin (selective for CYP3A enzymes) inhibited the demethylations of both antiprogestins by up to 77%. Rabbit polyclonal antibodies to CYP3A4 decreased initial rates of N-demethylation of the antihormones by up to 82%, whereas antibodies to CYP2C9 were not inhibitory. Collectively, these data thus suggest potential drug–drug interactions of these promising new therapeutic agents with concomitantly administered CYP3A4 substrates.

Footnotes

  • Send reprint requests to: Dr. Leslie Z. Benet, Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, 513 Parnassus Avenue, San Francisco, CA 94143-0446.

  • ↵1 Present address: Institut National de la Santé et de la Recherche Médicale, U-128, Route de Mende–B.P. 5051 (CNRS), 34033 Montpellier, France.

  • This study was supported in part by the National Institutes of Health GM26691 and was presented at the 10th Annual Meeting of the American Association of Pharmaceutical Scientists, Seattle, WA, 1996. G.R.J. was a fellow of the American Foundation for Pharmaceutical Education–Johnson & Johnson when this work was performed.

  • ↵3 S. A. Wrighton, personal communication.

  • Abbreviations used are::
    CYP
    cytochrome P450
    DDC
    diethyldithiocarbamic acid
    TAO
    triacetyloleandomycin
    HL
    human liver
    IC50
    50% inhibitory concentration
    • Received January 13, 1997.
    • Accepted June 10, 1997.
  • 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
Vol. 25, Issue 10
1 Oct 1997
  • Table of Contents
  • 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.
Cytochrome P4503A4-Mediated N-Demethylation of the Antiprogestins Lilopristone and Onapristone
(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

Cytochrome P4503A4-Mediated N-Demethylation of the Antiprogestins Lilopristone and Onapristone

Graham R. Jang and Leslie Z. Benet
Drug Metabolism and Disposition October 1, 1997, 25 (10) 1119-1122;

Citation Manager Formats

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

Share
Research ArticleArticle

Cytochrome P4503A4-Mediated N-Demethylation of the Antiprogestins Lilopristone and Onapristone

Graham R. Jang and Leslie Z. Benet
Drug Metabolism and Disposition October 1, 1997, 25 (10) 1119-1122;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results and Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Functional Characterization of 29 CYP4F2 Variants
  • Exposure-toxicity relation of apatinib
  • ABC phenomenon potentiates anti-HCC efficacy
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