| Project/Area Number |
18K14978
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Teikyo University (2019-2021)
Kanazawa University (2018) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | フェニトイン / 抗てんかん薬 / ケトン食 / 多価不飽和脂肪酸 / 薬物体内動態 / 薬物代謝酵素 / 高脂質食 / 食事療法 / 薬物動態 |
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| Outline of Final Research Achievements |
The ketogenic diet is hyper high-fat/low-carbohydrate diet that helps to control seizures in patients with refractory epilepsy. Phenytoin is used for epilepsy, and phenytoin elimination is a saturable process obeying Michaelis-Menten kinetics. High-fat diet and high-fat/high-cholesterol diet may affect the expression and activity of drug-metabolizing enzymes. In this study, we clarified the effects of the ketogenic diet on phenytoin pharmacokinetics. In enzyme inhibition study, α-linolenic acid and linoleic acid contained in the ketogenic diet inhibited the metabolism of phenytoin. In vivo pharmacokinetic study, simultaneous administration of phenytoin and α-linolenic acid decreased the oral clearance of phenytoin. These results suggest that polyunsaturated fatty acids contained in the ketogenic diet are factors of the phenytoin pharmacokinetics fluctuation.
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| Academic Significance and Societal Importance of the Research Achievements |
フェニトイン薬物療法においてα-リノレン酸は注意すべき薬物-飲食物間相互作用となる可能性が示され、てんかん治療においてケトン食療法を併用する際は，ケトン食を構成する脂肪酸の割合や摂取量に注意を払う必要があることが提起された。
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