Factors of individual variability in onset of drug-induced liver injury

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15001
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Nagoya University
• Principal Investigator: Yokoi Tsuyoshi 名古屋大学, 医学系研究科, 教授 (70135226)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 薬物性肝障害、 / 個体差 / バイオマーカー / マイクロRNA / 抗てんかん薬 / 薬剤性肝障害 / 代謝多型

Outline of Final Research Achievements

Severe drug-induced liver injury has been reported in the drug development process and some marketing drugs, but its occurrence has large individual variability. I conducted fundamental research aimed at clarifying the cause. Our research group has reported drug-induced mouse models in ten different types of clinical drugs. For the antiepileptic drug carbamazepine-induced liver injury mouse model, time-dependent changes of the expression of plasma microRNA were investigated, then, found candidate microRNAs related to individual variability of liver injury and then found related signaling pathway candidates. The potential of microRNA targets to predict individual variability in onset of liver injury is being investigating. In the future, extrapolation to humans will be examined considering the species difference of microRNA target.

Free Research Field

毒性学、医薬品安全性学