Comprehensive analysis of the factors regulating the disposition of small molecules at organ and tissue levels

2014 Fiscal Year Final Research Report

• Project Area: Establishment of Integrative Multi-level Systems Biology and its Applications
• Project/Area Number: 23136101
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: The University of Tokyo
• Principal Investigator: KUSUHARA Hiroyuki 東京大学, 薬学研究科(研究院), 教授 (00302612)
• Co-Investigator(Kenkyū-buntansha): HISAKA Akihiro 千葉大学, 大学院薬学系研究科, 教授 (80420206) ; MAEDA Kazuya 東京大学, 大学院薬学系研究科, 講師 (00345258)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 体内動態 / 体内動態予測 / PET / 生理学的モデル / cluster newton method

Outline of Final Research Achievements

For deep understanding the drug disposition at multi-levels from the molecular level to the whole organism level, this project was aimed to develop a methodology for implementing the extrapolation from the molecular to the whole organism level, and vice versa. We investigated the determination of the scaling factors for individual intrinsic processes in the overall hepatic elimination using PET, and absolute extrapolation method of the xenobiotic detoxification activity at the protein expression level using LC-MS/MS. As a physiological model, we constructed a detailed gastrointestinal absorption model (translocation model) that reflects the complex structure and dynamics in the digestive tract. Introducing a “Cluster Newton Method” enabled parameter estimation in complex models. These achievements are expected to contribute to the elaboration of the prediction of pharmacokinetics.

Free Research Field

薬物動態学