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Extrapolation of In Vitro Metabolic and P-Glycoprotein-Mediated Transport Data to In Vivo by Modeling and Simulations

  • Motohiro Kato
  • Yoshihisa Shitara
  • Masato Kitajima
  • Tatsuhiko Tachibana
  • Masaki Ishigai
  • Toshiharu Horie
  • Yuichi Sugiyama
Chapter

Abstract

Recently, a prediction method using in vivo K i values for inhibitors of cytochrome P450 with a physiologically based pharmacokinetic modeling was proposed to improve the accuracy of the prediction. Also, a method to predict the alterations caused by drug–drug interactions mediated by intestinal cytochrome P450 3A4 or P-glycoprotein was introduced. In this chapter, these methods and computerized simulation method are shown.

Keywords

Substrate Drug PBPK Model Inhibitor Drug Drug Interaction Study Draft Guidance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Motohiro Kato
    • 1
  • Yoshihisa Shitara
    • 2
  • Masato Kitajima
    • 3
  • Tatsuhiko Tachibana
    • 1
  • Masaki Ishigai
    • 1
  • Toshiharu Horie
    • 2
  • Yuichi Sugiyama
    • 4
  1. 1.Chugai Pharmaceutical Co. Ltd.GotembaJapan
  2. 2.Department of BiopharmaceuticsGraduate School of Pharmaceutical Sciences, Chiba UniversityChuo-kuJapan
  3. 3.Fujitsu Kyushu System Engineering Ltd.Sawara-kuJapan
  4. 4.Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of TokyoBunkyo-kuJapan

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