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Research on Drug-Induced Liver Injury Associated with MetabolicActivation by CYP

Research Project

Project/Area Number 22390020
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

HISAKA Akihiro  東京大学, 医学部附属病院, 特任准教授 (80420206)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Takehito  東京大学, 医学部附属病院, 助教 (00376469)
ITO Kousei  東京大学, 医学部附属病院, 助教 (30323405)
鈴木 洋史  東京大学, 医学部附属病院, 教授 (80206523)
Co-Investigator(Renkei-kenkyūsha) HONMA Masashi  東京大学, 医学部附属病院, 助教 (60401072)
IKEBUCHI Yuki  東京大学, 医学部附属病院, 助教 (20645725)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2010: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Keywords医薬品化学 / 薬剤性肝障害 / 炎症性サイトカイン / 療・福祉 / トランスレーショナルリサーチ / 蛋白質 / 薬剤反応性 / 臨床 / 医療・福祉
Research Abstract

In our previous study, the decrease of glutathione and the increase of four inflammatory cytokines in blood were identified as nongenetic risk factors of drug induced liver injury (DILI) in patients. In this study, cell toxicity was evaluated using rat primary isolated hepatocytes in the presence and the absence of these risk factors for 223 drugs, and it was revealed that the ratio correlated well with the observed risk of DILI in human. This method was superior to the standard method based on the amount of protein adducts, and would be useful for new drug development in the near future.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (18 results)

All 2012 2011 2010 Other

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (10 results) Remarks (6 results)

  • [Journal Article] 薬物動態解析プログラムNaPPの紹介2011

    • Author(s)
      樋坂章博
    • Journal Title

      薬剤学

      Volume: 2011 Pages: 168-178

    • NAID

      10029415959

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Theoretical considerations on quantitative prediction of drug-drug Interactions.2010

    • Author(s)
      Hisaka A, Ohno Y, Yamamoto T, Suzuki H
    • Journal Title

      Drug Metab Pharmacokinet

      Volume: 25 Pages: 48-61

    • NAID

      10027581845

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Predicting High-Risk Patients for the Onset of Drug-Induced Liver Injury2012

    • Author(s)
      Takaaki Ishida, Yuki Ikebuchi, Masashi Honma, Kousei Ito, Hiroshi Suzuki
    • Organizer
      日本薬物動態学会第27回年会
    • Related Report
      2012 Final Research Report
  • [Presentation] 患者の疾患背景に基づいた薬物誘発性肝障害の発症リスク評価2012

    • Author(s)
      池淵祐樹、伊藤晃成、本間雅、山本武人、鈴木洋史
    • Organizer
      第12回東京大学生命科学シンポジウム
    • Place of Presentation
      東京(東京大学)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 薬物間相互作用予測におけるPISCSの活用2011

    • Author(s)
      樋坂章博
    • Organizer
      CBI学会第322回研究講演会
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2011-12-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] Prediction of Clearance Changes of Drugs that are Substrates of Major Cytochrome P450 Enzymes Caused by Drug-Drug Interaction or Single Nucleotide Polymorphism2011

    • Author(s)
      Hisaka A, Ohno Y, Yamaguchi R, Ueno M, Ito K, Suzuki H
    • Organizer
      17th North American ISSX Meeting
    • Place of Presentation
      Atlanta, USA
    • Related Report
      2011 Annual Research Report
  • [Presentation] Significance of intestinal metabolism for various substrate drugs of CYP3A42011

    • Author(s)
      Hisaka A, Tsukihashi A, Suzuki H
    • Organizer
      International Symposium on BA/BE of Oral Drugs Products
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2011 Annual Research Report
  • [Presentation] Calculation of Unambiguous Intestinal Availability from Drug-drug Interaction2011

    • Author(s)
      Hisaka A, Tsukihashi A, Suzuki H
    • Organizer
      4th APISSX
    • Place of Presentation
      Tainan, Taiwan
    • Related Report
      2011 Annual Research Report
  • [Presentation] Discrimination of hepatic and intestinal contributions to drug-drug interaction mediated by inhibition of CYP3A42011

    • Author(s)
      Koh, S, Hisaka A,, Mori A, Suzuki H
    • Organizer
      26th JSSX meeting
    • Place of Presentation
      Hiroshima, Japan
    • Related Report
      2011 Annual Research Report
  • [Presentation] PISCS (pharmacokinetic interaction significance classification system) : to ward seamless drug-interaction alert (symposium)2010

    • Author(s)
      Hisaka A
    • Organizer
      Pharmaceutical sciences world_ congress (PSWC 2010)
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] Expressions of Hepatic Cytochrome P450 May be Regulated Dynamically and Cooperatively2010

    • Author(s)
      Hisaka A, Sasaki Y, Suzuki H
    • Organizer
      9th International Meeting of ISSX (2010)
    • Place of Presentation
      Istanbul, Turkey
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nappによるモデリンクとシミュレーションの紹介(シンポジスト)2010

    • Author(s)
      樋坂章博
    • Organizer
      第3回日本ファーマコメトリクス研究会
    • Place of Presentation
      東京
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://square.umin.ac.jp/todaiyak/gaiyou.htm

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.h.u-tokyo.ac.jp/research/center22/contribute/yakuri.html#kenkyu

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.h.u-tokyo.ac.jp/research/center22/index.html#katsudo

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://square.umin.ac.jp/todaiyak/gaiyou.htm

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.h.u-tokyo.ac.jp/research/center22/contribute/yakuri.html#kenkyu

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.h.u-tokyo.ac.jp/research/center22/index.html#katsudo

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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