Analysis of the relationship between P-glycoprotein-mediated interactions with androgens and their effects on the central nervous system

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16053
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Takasaki University of Health and Welfare
• Principal Investigator: Mizoi Kenta 高崎健康福祉大学, 薬学部, 博士研究員 (70849546)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 薬物-生体内基質間相互作用 / P-糖タンパク質 / アンドロゲン / 中枢作動薬 / 血液脳関門

Outline of Final Research Achievements

The aim of this study was to determine whether P-glycoprotein (P-gp)-mediated drug-endogenous substrates interactions (DEIs) with androgens can occur in vivo. Cell-based studies have identified several drugs, including centrally acting drugs, that can interact with androgens. Moreover, animal studies with these drugs revealed that the brain permeation of androgens is affected by DEI. This study indicates that P-gp-mediated DEI can occur at blood-brain barrier in vivo.

Free Research Field

生物薬剤学

Academic Significance and Societal Importance of the Research Achievements

相互作用は医薬品どうしによるものが一般的に知られており、その飲み合わせの注意喚起が行われている。本研究の成果から、医薬品どうしの相互作用だけではなく、生体内基質と医薬品のP-gpを介した相互作用は生体内基質の体内動態に影響を及ぼす可能性が示唆された。そのため、生体内基質との相互作用を考慮した医薬品の新しい注意喚起 (添付文書への記載の追加や修正など) が行われると期待される。