| Project/Area Number |
18K06758
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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 | Keio University |
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Principal Investigator |
Ohtani Hisakazu 慶應義塾大学, 薬学部(芝共立), 教授 (70262029)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 薬物相互作用 / 遺伝子多形 / cytochrome P450 / 個人差 / 代謝酵素 / トランスポーター / 飲食物成分 / グレープフルーツ / シトクロムP450 / OATPs / 代謝阻害 / 果汁 / ジャバラ / 遺伝子多型 / トランスポータ / CYP2C / 飲食物 / 個別化医療 |
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| Outline of Final Research Achievements |
The mechanism of food-drug interactions includes the inhibition of metabolic enzymes or drug transporters, which have genetic variations. The aim of this study is to clarify whether the genetic variations of metabolic enzymes and transporters lead to the altered inhibitory kinetics of respective inhibitors contained in a variety of fruit juices. We focused upon two metabolic enzymes (CYP2C9 and CYP2C19) and two transporters (OATP1A2 and OATP2B1). Detailed analysis revealed that the inhibitory kinetics of various inhibitors highly differ among genetic variants. Therefore, the genetic variants of metabolic enzymes and drug transporters are considered to be one of the important factors to confer inter-individual variation in the extent of food-drug interactions. We also succeeded in identifying a novel OATP inhibitor, narirutin, from grape fruit juice.
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| Academic Significance and Societal Importance of the Research Achievements |
薬物相互作用 (いわゆる「薬の飲み合わせ」) のリスクが高い患者と低い患者が存在する原因について、代表的な薬物相互作用の機構に関係する「代謝酵素」と「輸送担体」の遺伝的な違いに着目してアプローチを試みた研究である。
代謝酵素や輸送担体の遺伝的な違いが、飲食物成分に対する感受性の差をもたらしていることを定量的に明らかにするとともに、果汁中より新たな相互作用原因成分を同定することにも成功しており、薬物相互作用の予測と回避に重要な情報を提供する研究である。
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