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Research ArticleArticle
Open Access

Revisiting Nonlinear Bosentan Pharmacokinetics by Physiologically Based Pharmacokinetic Modeling: Target Binding, Albeit Not a Major Contributor to Nonlinearity, Can Offer Prediction of Target Occupancy

Satoshi Koyama, Kota Toshimoto, Wooin Lee, Yasunori Aoki and Yuichi Sugiyama
Drug Metabolism and Disposition April 2021, 49 (4) 298-304; DOI: https://doi.org/10.1124/dmd.120.000023
Satoshi Koyama
Sugiyama Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, Yokohama, Kanagawa, Japan (S.K., K.T., Y.S.); College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Gwanak-gu, Seoul, Korea (W.L.); and National Institute of Informatics, Chiyoda-ku, Tokyo, Japan (Y.A.)
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Kota Toshimoto
Sugiyama Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, Yokohama, Kanagawa, Japan (S.K., K.T., Y.S.); College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Gwanak-gu, Seoul, Korea (W.L.); and National Institute of Informatics, Chiyoda-ku, Tokyo, Japan (Y.A.)
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Wooin Lee
Sugiyama Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, Yokohama, Kanagawa, Japan (S.K., K.T., Y.S.); College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Gwanak-gu, Seoul, Korea (W.L.); and National Institute of Informatics, Chiyoda-ku, Tokyo, Japan (Y.A.)
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Yasunori Aoki
Sugiyama Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, Yokohama, Kanagawa, Japan (S.K., K.T., Y.S.); College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Gwanak-gu, Seoul, Korea (W.L.); and National Institute of Informatics, Chiyoda-ku, Tokyo, Japan (Y.A.)
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Yuichi Sugiyama
Sugiyama Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, Yokohama, Kanagawa, Japan (S.K., K.T., Y.S.); College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Gwanak-gu, Seoul, Korea (W.L.); and National Institute of Informatics, Chiyoda-ku, Tokyo, Japan (Y.A.)
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Article Information

vol. 49 no. 4 298-304
DOI 
https://doi.org/10.1124/dmd.120.000023
PubMed 
33558262

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0090-9556
Online ISSN 
1521-009X
History 
  • Received March 20, 2020
  • Accepted January 15, 2021
  • Published online March 10, 2021.

Article Versions

  • Earlier version (February 8, 2021 - 08:24).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2021 The Author(s) This is an open access article distributed under the CC BY Attribution 4.0 International license.

Author Information

  1. Satoshi Koyama,
  2. Kota Toshimoto1,
  3. Wooin Lee,
  4. Yasunori Aoki2, and
  5. Yuichi Sugiyama
  1. Sugiyama Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, Yokohama, Kanagawa, Japan (S.K., K.T., Y.S.); College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Gwanak-gu, Seoul, Korea (W.L.); and National Institute of Informatics, Chiyoda-ku, Tokyo, Japan (Y.A.)
  1. Address correspondence to:
    Dr. Yuichi Sugiyama, Sugiyama Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, Kanagawa 230-0045, Japan. E-mail: ychi.sugiyama{at}riken.jp
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Drug Metabolism and Disposition: 49 (4)
Drug Metabolism and Disposition
Vol. 49, Issue 4
1 Apr 2021
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Research ArticleArticle

Target Occupancy of Bosentan Estimated by PBPK Modeling

Satoshi Koyama, Kota Toshimoto, Wooin Lee, Yasunori Aoki and Yuichi Sugiyama
Drug Metabolism and Disposition April 1, 2021, 49 (4) 298-304; DOI: https://doi.org/10.1124/dmd.120.000023

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Research ArticleArticle

Target Occupancy of Bosentan Estimated by PBPK Modeling

Satoshi Koyama, Kota Toshimoto, Wooin Lee, Yasunori Aoki and Yuichi Sugiyama
Drug Metabolism and Disposition April 1, 2021, 49 (4) 298-304; DOI: https://doi.org/10.1124/dmd.120.000023
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