Comprehensive analysis of the factors regulating the disposition of small molecules at organ and tissue levels
| 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 |
|
|---|
| 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
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥30,420,000 (Direct Cost: ¥23,400,000、Indirect Cost: ¥7,020,000)
Fiscal Year 2014: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2013: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2012: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
|
|---|
| Keywords | 体内動態 / 体内動態予測 / PET / 生理学的モデル / cluster newton method / 薬物動態学 / 薬物間相互作用 / 代謝物 / クラスターニュートン法 / トランスロケーションモデル / 薬物動態 / 肝異物解毒システム / スケーリングファクター / 階層構造 / 代謝酵素 / トランスポーター / ＰＥＴ |
|---|
| 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.
|
Report
(5 results)
Research Products
(50 results)
-
-
[Journal Article] Involvement of Organic Cation Transporters in the Clearance and Milk Secretion of Thiamine in Mice.2015
Author(s)
Kato K, Moriyama C, Ito N, Zhang X, Hachiuma K, Hagima N, Iwata K, Yamaguchi JI, Maeda K, Ito K, Suzuki H, Sugiyama Y, Kusuhara H.
-
Journal Title
Related Report
Peer Reviewed / Acknowledgement Compliant
-
-
[Journal Article] Evaluation of Oatp and Mrp2 activities in hepatobiliary excretion using newly developed positron emission tomography tracer [11C]dehydropravastatin in rats.2013
Author(s)
Shingaki T, Takashima T, Ijuin R, Zhang X, Onoue T, Katayama Y, Okauchi T, Hayashinaka E, Cui Y, Wada Y, Suzuki M, Maeda K, Kusuhara H, Sugiyama Y, Watanabe Y.
-
Journal Title
J Pharmacol Exp Ther
Volume: 347
Issue: 1
Pages: 193-202
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
