Estimation of in vivo enzyme inhibition parameters for modelling analyses of drug interactions.
| Project/Area Number |
18K06799
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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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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Musashino University |
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Principal Investigator |
Ito Kiyomi 武蔵野大学, 薬学部, 教授 (60232435)
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| Co-Investigator(Kenkyū-buntansha) |
工藤 敏之 武蔵野大学, 薬学部, 講師 (10584815)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 薬物相互作用 / 生理学的薬物速度論モデル |
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| Outline of Final Research Achievements |
In the quantitative prediction of drug-drug interactions by model analysis, it is essential to set up appropriate models and parameters. Prediction accuracy is known to be low if the enzyme inhibition parameters obtained from in vitro studies are used for reversible inhibition of the typical drug-metabolizing enzyme cytochrome P450. The present study indicated that the prediction using in vitro inhibition parameters also results in underestimation for glucuronosyltransferase-mediated interactions and time-dependent enzyme inhibition. The method for scaling up in vitro metabolic inhibition parameters to in vivo should be further investigated.
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| Academic Significance and Societal Importance of the Research Achievements |
薬物相互作用による薬物動態の変動は、薬効や副作用の変動につながることから、相互作用の定量的な予測を目的としたモデル解析の活用頻度が高まっている。本研究では、臨床事例の多い薬物代謝酵素の阻害に基づく相互作用を対象とし、モデル解析による予測のための適切なパラメータ設定について新たな知見を得ることができた。本研究の成果は、医薬品開発の効率化および臨床での医薬品適正使用に資することが期待される。
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Report
(6 results)
Research Products
(38 results)
