Elucidation of pharmacokinetics fluctuation factors by ketogenic diet

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K14978
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Teikyo University (2019-2021); Kanazawa University (2018)
• Principal Investigator: Akashita Gaku 帝京大学, 薬学部, 助教 (90781542)
• Project Period (FY): 2018-04-01 – 2022-03-31
• 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

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.

Free Research Field

医療薬学

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。