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

Using expression data for quantification of active processes in physiologically-based pharmacokinetic modeling

Michaela Meyer, Sebastian Schneckener, Bernd Ludewig, Lars Kuepfer and Joerg Lippert
Drug Metabolism and Disposition January 31, 2012, dmd.111.043174; DOI: https://doi.org/10.1124/dmd.111.043174
Michaela Meyer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sebastian Schneckener
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernd Ludewig
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lars Kuepfer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: lars.kuepfer@bayer.com
Joerg Lippert
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Active processes involved in drug metabolization and distribution mediated by enzymes, transporters or binding partners mostly occur simultaneously in various organs. A quantitative description of active processes, however, is difficult due to a limited experimental accessibility of tissue-specific protein activity in vivo. In this work we present a novel approach to estimate in vivo activity of such enzymes or transporters which have an influence on drug pharmacokinetics. Tissue specific mRNA expression is used as a surrogate for protein abundance and activity and is integrated into physiologically-based pharmacokinetic (PBPK) models which already represent detailed anatomical and physiological information. The new approach was evaluated using three publicly available databases: Whole genome expression microarrays from ArrayExpress, RT-PCR derived gene expression estimates collected from literature, and expressed sequence tags (EST) from UniGene. Expression data were preprocessed and stored in a customized database that was then used to build PBPK models for pravastatin in humans. These models represented drug uptake by OATP1B1 and OAT3, active efflux by MRP2, and metabolization by sulfotransferases in either liver, kidney and/or intestine. Bench-marking of PBPK models based on gene expression data against alternative models with either less complex model structure or randomly assigned gene expression values clearly demonstrated the superior model performance of the former. Besides an accurate prediction of drug pharmacokinetics, integration of relative gene expression data in PBPK models offers the unique possibility to simultaneously investigate drug-drug interactions in all relevant organs due to the physiological representation of protein mediated processes.

  • bioinformatics
  • computational models
  • computer modeling and simulation
  • kinetic modeling
  • pharmacokinetic modeling
  • physiologically-based modeling
  • physiologically-based pharmacokinetics
  • transporters
  • Received October 5, 2011.
  • Accepted January 31, 2012.
  • The American Society for Pharmacology and Experimental Therapeutics
Next
Back to top

In this issue

Drug Metabolism and Disposition: 51 (10)
Drug Metabolism and Disposition
Vol. 51, Issue 10
1 Oct 2023
  • 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.
Using expression data for quantification of active processes in physiologically-based pharmacokinetic modeling
(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

Using expression data for quantification of active processes in physiologically-based pharmacokinetic modeling

Michaela Meyer, Sebastian Schneckener, Bernd Ludewig, Lars Kuepfer and Joerg Lippert
Drug Metabolism and Disposition January 31, 2012, dmd.111.043174; DOI: https://doi.org/10.1124/dmd.111.043174

Citation Manager Formats

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

Share
Research ArticleArticle

Using expression data for quantification of active processes in physiologically-based pharmacokinetic modeling

Michaela Meyer, Sebastian Schneckener, Bernd Ludewig, Lars Kuepfer and Joerg Lippert
Drug Metabolism and Disposition January 31, 2012, dmd.111.043174; DOI: https://doi.org/10.1124/dmd.111.043174
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • 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