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 ArticlePerspective

Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidances from Regulatory Agencies: Focus on Down-regulation, CYP2C Induction and CYP2B6 Positive Control

Niresh Hariparsad, Diane Ramsden, Jairam Palamanda, Joshua G Dekeyser, Odette A Fahmi, Jane R Kenny, Heidi Einolf, Michael Mohutsky, Magalie Pardon, Amy Y Siu, Liangfu Chen, Michael Sinz, Barry Jones, Robert Walsky, Shannon Dallas, Suresh K Balani, George Zhang, David Buckley and Donald Tweedie
Drug Metabolism and Disposition June 23, 2017, dmd.116.074567; DOI: https://doi.org/10.1124/dmd.116.074567
Niresh Hariparsad
1 Vertex Pharmaceuticals;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: niresh_hariparsad@vrtx.com
Diane Ramsden
2 Boehringer Ingelheim;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jairam Palamanda
3 Merck and Co;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joshua G Dekeyser
4 Amgen;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Odette A Fahmi
5 Pfizer;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jane R Kenny
6 Genentec;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heidi Einolf
7 Novartis;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Mohutsky
8 Eli Lilly;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Magalie Pardon
9 Sanofi;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amy Y Siu
10 Eisai;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Liangfu Chen
11 GSK;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Sinz
12 BMS;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Barry Jones
13 AstraZenecca;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert Walsky
14 EMD Serono;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shannon Dallas
15 Janssen R&D;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Suresh K Balani
16 Takeda;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
George Zhang
17 Corning Life Sciences;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Buckley
18 XenoTech LLC
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Donald Tweedie
3 Merck and Co;
  • 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 + SI
  • PDF
Loading

Abstract

The European Medicines Agency (EMA), the Pharmaceutical and Medical Devices Agency and the Food and Drug Administration have issued guidances for the conduct of drug-drug interaction (DDI) studies. To examine the applicability of these regulatory recommendations specifically for induction, a group of scientists, under the auspices of the Drug Metabolism Leadership Group of the Innovation and Quality (IQ) Consortium, formed the Induction Working Group (WG). A team of 20 scientists, from 16 of the 39 pharmaceutical companies, which are members of the IQ Consortium, and three Contract Research Organizations, reviewed the recommendations, focusing initially on the current EMA guidance. Questions were collated from IQ member companies as to which aspects of the guidance required further evaluation. The EMA was then approached to provide insights into their recommendations on the following points; a) evaluation of down-regulation, b) in vitro assessment of CYP2C induction, c) the recommendation to use CITCO as the positive control for CYP2B6 induction, d) data interpretation (two-fold increase in mRNA as evidence of induction), and e) duration of incubation of hepatocytes with test article. The Induction WG conducted an anonymous survey among IQ member companies to query current practices, specifically focusing on how the aforementioned key points are evaluated. Responses were received from 19 companies. All data/information was blinded prior to being shared with the Induction WG. The results of the survey are presented together with consensus recommendations on down-regulation, CYP2C induction and CYP2B6 positive control. Data interpretation and incubation duration will be reported in subsequent manuscripts.

  • drug-drug interactions
  • enzyme induction
  • in vitro-in vivo prediction (IVIVE)
  • The American Society for Pharmacology and Experimental Therapeutics
Next
Back to top

In this issue

Drug Metabolism and Disposition: 51 (2)
Drug Metabolism and Disposition
Vol. 51, Issue 2
1 Feb 2023
  • 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.
Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidances from Regulatory Agencies: Focus on Down-regulation, CYP2C Induction and CYP2B6 Positive Control
(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 ArticlePerspective

Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidances from Regulatory Agencies: Focus on Down-regulation, CYP2C Induction and CYP2B6 Positive Control

Niresh Hariparsad, Diane Ramsden, Jairam Palamanda, Joshua G Dekeyser, Odette A Fahmi, Jane R Kenny, Heidi Einolf, Michael Mohutsky, Magalie Pardon, Amy Y Siu, Liangfu Chen, Michael Sinz, Barry Jones, Robert Walsky, Shannon Dallas, Suresh K Balani, George Zhang, David Buckley and Donald Tweedie
Drug Metabolism and Disposition June 23, 2017, dmd.116.074567; DOI: https://doi.org/10.1124/dmd.116.074567

Citation Manager Formats

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

Share
Research ArticlePerspective

Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidances from Regulatory Agencies: Focus on Down-regulation, CYP2C Induction and CYP2B6 Positive Control

Niresh Hariparsad, Diane Ramsden, Jairam Palamanda, Joshua G Dekeyser, Odette A Fahmi, Jane R Kenny, Heidi Einolf, Michael Mohutsky, Magalie Pardon, Amy Y Siu, Liangfu Chen, Michael Sinz, Barry Jones, Robert Walsky, Shannon Dallas, Suresh K Balani, George Zhang, David Buckley and Donald Tweedie
Drug Metabolism and Disposition June 23, 2017, dmd.116.074567; DOI: https://doi.org/10.1124/dmd.116.074567
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
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Regulatory Guidance for P450 Induction from IQ: Part 3
  • Prioritizing NPs as precipitants of NPDIs
Show more Perspective

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