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

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670071
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: The 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
• 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

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.

Free Research Field

分子薬物動態学