Quantitative prediction of bioavailability and drug-drug interactions of orally administered drugs
| Project/Area Number |
26460204
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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) |
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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥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 / 薬物相互作用 / 定量的予測 / 相互作用 / CYP3A4 |
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| Outline of Final Research Achievements |
The present study aimed to improve a model to quantitatively predict the bioavailability and drug-drug interactions for orally administered CYP3A substrates. Alprazolam (ALP), midazolam (MDZ) and triazolam (TRZ) were used as CYP3A substrates, and ritonavir (RIT) and erythromycin (ERY) were used as CYP3A inhibitors. Metabolic and inhibition parameters of those drugs were obtained in in vitro studies. Transfer parameters in the intestinal epithelial cells were also estimated in vitro using Caco-2 cells. The obtained parameters were incorporated into an ITAM-PK model to predict the oral bioavailability of ALP, MDZ and TRZ, and also interactions between CYP3A substrates and CYP3A inhibitors.
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Report
(4 results)
Research Products
(12 results)
