Quantitative prediction of oral bioavailability independent of metabolic pathway
| Project/Area Number |
17K08423
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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 | Kitasato University |
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Principal Investigator |
ITOH Tomoo 北里大学, 薬学部, 教授 (30223168)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 経口投与 / バイオアベイラビリティ / 薬物間相互作用 / 定量的予測 / 薬物動態 / グルクロン酸抱合 / 相互作用 / 薬学 |
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| Outline of Final Research Achievements |
ITAM-PK model was developed to quantitatively predict oral bioavailability and drug-drug interactions for orally administered CYP3A4 substrates. The present study aimed to apply the model to quantitatively predict the bioavailability and drug-drug interactions for the substrates that are metabolized by enzymes other than CYP3A4. Oral bioavailability of CYP1A2 substrates, tizanidine and theophylline, were reasonably well predicted. For propranolol, cellular binding of the substrate needs to be incorporated to predict oral bioavailability. Drug-drug interactions (DDI) between tizanidine and fluvoxamine, a CYP1A2 inhibitor, were quantitatively predicted very well. On the other hand, DDI between tizanidine and ciprofloxacin, another CYP1A2 inhibitor, was not well predicted.
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| Academic Significance and Societal Importance of the Research Achievements |
試験管内の実験データをもとに、薬物を経口投与のバイオアベイラビリティや薬物間相互作用を定量的に予測することができれば、医薬品開発の無駄をなくし、ヒトに投与する前に薬物間相互作用を回避することが可能となる。
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Report
(4 results)
Research Products
(11 results)
