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

Human Hepatocytes in Primary Culture Predict Lack of Cytochrome P-450 3A4 Induction by Eletriptan In Vivo

Lydiane Pichard-Garcia, Ruth Hyland, Jean Baulieu, Jean-Michel Fabre, Ashley Milton and Patrick Maurel
Drug Metabolism and Disposition January 2000, 28 (1) 51-57;
Lydiane Pichard-Garcia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ruth Hyland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean Baulieu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Michel Fabre
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ashley Milton
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick Maurel
  • 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

Eletriptan (Relpax) is a novel 5-hydroxytryptamine (serotonin)1D/1B agonist currently in development for the acute treatment of migraine. The aim of this work was to evaluate the relative induction potency of eletriptan in vitro compared with well characterized cytochrome P-450 (CYP) inducers with primary cultures of human hepatocytes and to relate this to the situation in vivo. Eletriptan was a weak inducer of CYP3A4 protein and cyclosporin A oxidation in four of the six cultures used, whereas rifampicin was a potent inducer in all cultures. Induction was concentration dependent and not detectable at eletriptan concentrations of 5 μM and lower. The amplitude of the increase in CYP3A4 protein and activity by 25 μM eletriptan was significantly lower, with a mean of 19 (P = .0015) and 26% (P = .0002), respectively, of that observed in response to 25 μM rifampicin. CYP2A6, a protein with minor pharmacological implication, also was induced by eletriptan and rifampicin in two cultures but was not detected in the others. The levels of other CYP proteins, including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, were not affected by eletriptan. Because the maximum blood concentration of eletriptan in humans after a therapeutic dose (maximum 80 mg) is 0.5 μM, the in vitro model would predict no clinically significant induction of CYP3A4 protein in vivo. This has been confirmed subsequently in a clinical study, with 6β-hydroxycortisol/cortisol ratios as marker of CYP3A4 activity. Eletriptan is therefore not an inducer of CYP3A4 at clinical doses.

Footnotes

  • Send reprint requests to: Dr. Patrick Maurel, Institut National de la Santé et de la Recherche Médicale U128, Centre National de la Recherche Scientifique IFR24, 1919 Route de Mende, 34293 Montpellier (Cedex 05), France. E-mail:maurel{at}u128.crbm.cnrs-mop.fr

  • Abbreviations used are::
    CYP
    cytochrome P-450
    RIF
    rifampicin
    TCDD
    2,3,7,8-tetrachlorodibenzo(p)dioxin
    DMSO
    dimethyl sulfoxide
    ECL
    enhanced chemiluminescence
    GAPDH
    glyceraldehyde 6-phosphate dehydrogenase
    • Received July 9, 1999.
    • Accepted September 27, 1999.
  • 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: 28 (1)
Drug Metabolism and Disposition
Vol. 28, Issue 1
1 Jan 2000
  • 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.
Human Hepatocytes in Primary Culture Predict Lack of Cytochrome P-450 3A4 Induction by Eletriptan In Vivo
(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

Human Hepatocytes in Primary Culture Predict Lack of Cytochrome P-450 3A4 Induction by Eletriptan In Vivo

Lydiane Pichard-Garcia, Ruth Hyland, Jean Baulieu, Jean-Michel Fabre, Ashley Milton and Patrick Maurel
Drug Metabolism and Disposition January 1, 2000, 28 (1) 51-57;

Citation Manager Formats

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

Share
Research ArticleArticle

Human Hepatocytes in Primary Culture Predict Lack of Cytochrome P-450 3A4 Induction by Eletriptan In Vivo

Lydiane Pichard-Garcia, Ruth Hyland, Jean Baulieu, Jean-Michel Fabre, Ashley Milton and Patrick Maurel
Drug Metabolism and Disposition January 1, 2000, 28 (1) 51-57;
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
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
  • Biotransformation of Trastuzumab and Pertuzumab
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