Searching for endogenous substrates of organic cation transporters by selective metabolomics

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06745
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Kanazawa University
• Principal Investigator: Masuo Yusuke 金沢大学, 薬学系, 助教 (90708140)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: メタボローム解析 / 有機カチオン膜輸送体 / バイオマーカー / 膜輸送体 / メタボロミクス / 生体内基質

Outline of Final Research Achievements

Organic cation transporters (OCTs) are involved in hepatic and renal distribution of various substrates, and may be primarily involved in pharmacokinetics of some substrate drugs. The aim of the present study is to search endogenous OCTs substrates. According to the untargeted metabolome analysis, plasma concentration of some acylcarnitines in OCT’s inhibitors treated mice were higher than that in vehicle-treated mice. Efflux of acetylcarnitine was also observed in from oocytes expressing OCT1. Thus, acylcarnitines were presumably endogenous OCT1 substrates although the role of OCTs in their tissue distribution should be further evaluated.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

膜輸送体OCTsの輸送機能は、先天的・後天的な要因で個人差があり、輸送機能をin vivoで個人毎に予測することは、薬物治療上重要である。OCTsの生体内基質は、その血漿中濃度を測定することで、薬物相互作用または個人差に起因するOCTs輸送活性の変化をin vivoで予測可能にし、OCTs基質薬による適切な薬物治療を可能にする。本研究で同定したバイオマーカー候補として、血漿中acylcarnitine濃度は、薬物相互作用予測や、機能変化時の適切な基質薬の投与量設計に応用できる。