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2012 Fiscal Year Final Research Report

Prediction of interindividual differences of drug metabolism and pharmacokinetics using chimeric mice with humanized liver

Research Project

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Project/Area Number 23659053
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionHiroshima University

Principal Investigator

OHTA Shigeru  広島大学, 大学院・医歯薬保健学研究院, 教授 (60160503)

Co-Investigator(Kenkyū-buntansha) SANOH Seigo  広島大学, 大学院・医歯薬保健学研究院, 助教 (00552267)
Research Collaborator FUJIMOTO Mami  広島大学, 薬学部, 学生
Project Period (FY) 2011 – 2012
Keywords薬学 / ヒト肝細胞移植キメラマウス / 肝細胞 / 薬物代謝酵素 / 遺伝多型 / 薬物動態
Research Abstract

Recently, intra-individual differences of drug metabolism and pharmacokinetics caused by the polymorphism of drug metabolic enzymes have been concerned in drug development. It is difficult to use drugs which show interindividual differencesbecause these result in changes of efficacy and safety. We used chimeric mice transplanted with human donor hepatocytes to examine whether chimeric mice reflect drug metabolism and pharmacokinetics of donors. In the results, it is possible to become useful models to predict interindividual differences of drug metabolism and pharmacokinetics.

  • Research Products

    (9 results)

All 2013 2012 2011

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (4 results)

  • [Journal Article] Prediction of human metabolism of thesedative-hypnotic zaleplonusing chimeric mice transplanted with human hepatocytes2013

    • Author(s)
      Tanoue C, Sugihara K, Uramaru N, Tayama Y,Watanabe Y, Horie T, Ohta S,Kitamura S
    • Journal Title

      Xenobiotica

      Pages: in press

    • Peer Reviewed
  • [Journal Article] 2,5-Dihydroxy-4-methoxybenzophenone: a novelmajorin vitro metabolite of benzophenone-3formed by rat and human liver microsomes2013

    • Author(s)
      Kamikyouden N, Sugihara K, Watanabe Y,Uramaru N, Murahashi T, Kuroyanagi M,Sanoh S, Ohta S, Kitamura S
    • Journal Title

      Xenobiotica

      Volume: 43(6) Pages: 514-9

    • Peer Reviewed
  • [Journal Article] Predictability of metabolism of ibuprofen and naproxen using chimeric mice with human hepatocytes2012

    • Author(s)
      Sanoh S, Horiguchi A, Sugihara K, Kotake Y, Tayama Y, Uramaru N, Ohshita H,Tateno C, Horie T, Kitamura S, Ohta S
    • Journal Title

      Drug MetabDispos

      Volume: 40(12) Pages: 2267-72

    • Peer Reviewed
  • [Journal Article] Prediction of in vivo hepatic clearance andhalf-life of drug candidates in human using chimeric mice with humanized liver2012

    • Author(s)
      Sanoh S, Horiguchi A, Sugihara K, Kotake Y, Tayama Y, Ohshita H, Tateno C,Horie T, Kitamura S, Ohta S
    • Journal Title

      Drug MetabDispos

      Volume: 40(2) Pages: 322-8

    • Peer Reviewed
  • [Journal Article] Prediction ofhuman metabolism of FK3453 by aldehyde oxidase using chimeric mice transplantedwith human or rat hepatocytes2012

    • Author(s)
      Sanoh S, Nozaki K, Murai H, Terashita S, Teramura T, Ohta S
    • Journal Title

      Drug MetabDispos

      Volume: 40(1) Pages: 76-82

    • Peer Reviewed
  • [Presentation] ヒト肝細胞移植キメラマウスにおけるアロメトリックスケーリングを用いたヒト体内動態予測2013

    • Author(s)
      藤本真美, 佐能正剛,成富洋一,佐藤公也,河村章生,堀口 彩,杉原数美,立野知世,堀江 透,北村繁幸,太田 茂
    • Organizer
      日本薬学会 133 年会
    • Place of Presentation
      横浜
    • Year and Date
      20130327-31
  • [Presentation] ヒト肝細胞移植キメラマウスにおけるアロメトリックスケーリングを用いた血中動態予測性の検証2012

    • Author(s)
      藤本真美,佐能正剛,成富洋一,佐藤公也,河村章生,堀口 彩,杉原数美,立野知世,堀江 透,北村繁幸,太田 茂
    • Organizer
      日本薬物動態学会第27 年会
    • Place of Presentation
      東京
    • Year and Date
      20121120-22
  • [Presentation] Prediction of human pahemacokinetics by allometric scaling using chimeric mice with humanized liver2012

    • Author(s)
      Sanoh S, Naritomi Y, Sato K, Kawamura A, Horiguchi A, Sugihara K, Tateno C, HorieT, Kitamura S, Ohta S.
    • Organizer
      19thInternational Symposium on Microsomes and Drug Oxidations and 12thEuropean Regional International Society for the Study of Xenobiotics meeting
    • Place of Presentation
      Noordwijkaan Zee (オランダ)
    • Year and Date
      20120617-21
  • [Presentation] Prediction of PK parameters of human using human chimeric mice.2011

    • Author(s)
      Sanoh S, Horiguchi A, Sugihara K, Tateno C, Horie T, Kitaura S, Ohta S.
    • Organizer
      17thInternational Society for the Study of Xenobiotics North American Meeting
    • Place of Presentation
      Atlanta(アメリカ)
    • Year and Date
      20111016-20

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Published: 2014-09-25  

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