Prediction of interindividual variability about adverse effect caused by molecular target drugs using physiologacal mechanism based mathematical model
| Project/Area Number |
18K14971
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Toshimoto Kota 国立研究開発法人理化学研究所, 科技ハブ産連本部, 特別研究員 (70740504)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | モデリング＆シミュレーション / 生理学的薬物速度論モデル / 仮想臨床試験 / 薬物相互作用 / 薬物動態学 / 遺伝子多型 / モデリング＆シミュテーション / 個人間変動 / 分子標的薬 |
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| Outline of Final Research Achievements |
The focused drug in this research was changed from molecular target drugs to antidiabetic drug (repaglinide) because it was difficult to establish the mathematical model of the molecular target drugs which could reproduce clinical reported drug concentration-time profiles. There are some clinical reports that the concentration of repaglinide in blood is increased by the coadministration of gemfibrozil (hyperlipidemia drug). Virtual subjects were generated on the computer by considering interindividual variability of physiological and physicochemical parameters in the mathematical model of repaglinide. Using these virtual subjects, the concentration-time profile of repaglinide coadministered with gemfibrozil for each virtual subject was simulated. Comparing the simulation results to clinical data, simulation results well reproduced clinical observed data.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果に、別途構築した薬物毒性の数理モデルを組み合わせることにより、その薬物の薬効および副作用発生頻度をシミュレーションすることが可能となる。その結果に基づいて、新規医薬品開発における臨床試験の試験デザインの最適化、薬効を最大限引き出しつつ副作用の発生を抑える最適な薬物投与量を推定することが可能になる。
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Report
(3 results)
Research Products
(1 results)
