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Analysis of pharmacokinetics and toxicological effects of drugs by quantitative estimation of human biliary excretion of drugs at a single cell level

Research Project

Project/Area Number 25670071
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

MAEDA Kazuya  東京大学, 薬学研究科(研究院), 講師 (00345258)

Co-Investigator(Kenkyū-buntansha) MASUJIMA Tsutomu  理化学研究所, 生命システム研究センター, チームリーダー (10136054)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords肝細胞 / 薬物動態 / トランスポーター / 質量分析計 / 一分子測定 / sandwich培養 / LC-MS/MS / 胆汁排泄 / HepaRG細胞
Outline of Final Research Achievements

The purpose of this study is to optimizing the experimental conditions for quantifying the drug movement in sandwich cultured hepatocytes by utilizing the novel technique of measuring the substances in a single cell with high-spec mass spectrometry. As a result, we succeeded in guiding a sample collecting probe to the bile pocket and confirming the sample collection in the bile pocket by using fluorescent compounds efficiently accumulated in the bile pocket in parallel. However, matrigel layer may inhibit the passage of probe to the bile pocket and we should improve this point for the highly sensitive measurement of compounds in this system. We found that HepaRG cells could efficiently form bile pockets between cells without any gels and excretion of several drugs into bile pocket could be observed in HepaRG cells. Thus, the use of alternative cell lines such as HepaRG cells may overcome the current problem.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (2 results)

All 2014

All Presentation (2 results) (of which Invited: 2 results)

  • [Presentation] 薬物動態の予測におけるヒト組織活用の意義2014

    • Author(s)
      前田和哉
    • Organizer
      第4回レギュラトリーサイエンス学会学術大会
    • Place of Presentation
      東京都千代田区
    • Year and Date
      2014-09-04 – 2014-09-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Demonstration and Prediction of Clinical Importance of Drug Transporters as Determinants of Hepatic Clearance of Anionic Drugs2014

    • Author(s)
      前田和哉
    • Organizer
      5th Asia Pasific ISSX meeting
    • Place of Presentation
      Tianjin, China
    • Year and Date
      2014-05-10 – 2014-05-12
    • Related Report
      2014 Annual Research Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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