Physiologically based pharmacokinetic analysis for predicting drug interactions involving hepatic uptake and metabolism.
| Project/Area Number |
26460209
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Musashino University |
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Principal Investigator |
Ito Kiyomi 武蔵野大学, 薬学研究所, 教授 (60232435)
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| Co-Investigator(Kenkyū-buntansha) |
工藤 敏之 武蔵野大学, 薬学研究所, 講師 (10584815)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 薬物相互作用 / 生理学的薬物速度論モデル / 緩衝液条件 / CYP3A4 / CYP2C8 / OATP1B1 / 薬物代謝酵素 / ヒト肝ミクロソーム |
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| Outline of Final Research Achievements |
For drugs metabolized by multiple enzymes, precise estimation of the contribution of each metabolic enzyme is important in evaluating the effects of metabolic inhibition by co-administered drugs. Importance of paying attention to the buffer condition in in vitro metabolic studies was confirmed by our study investigating the contribution of CYP2C8 and CYP3A4 in the metabolism of repaglinide. In addition, a physiologically based pharmacokinetic (PBPK) modeling analysis demonstrated the involvement of both hepatic uptake inhibition and metabolic inhibition in the interaction between clarithromycin and glibenclamide. Similar PBPK analyses as in the present study are expected to facilitate the efficiency in drug development and to provide security in medication involving multiple drugs.
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Report
(4 results)
Research Products
(33 results)
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[Presentation] Drug interaction guideline for drug development and labeling recommendations: final draft of Japanese new guideline.2014
Author(s)
Y. Saito, A. Hisaka, T. Kume, K. Maeda, H. Suzuki, K. Ito, K. Inui, Y. Kato, S. Ozawa, H. Watanabe, S. Miura, T. Mitsuoka, K. Maekawa, M. Sato, A. Ishiguro, R. Sato, N. Nagai, Y. Ohno
Organizer
19th North American ISSX meeting/29th JSSX meetimg
Place of Presentation
19th North American ISSX meeting/29th JSSX meetimg
Year and Date
2014-10-19 – 2014-10-23
Related Report
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