Physiologically based pharmacokinetic analysis for predicting drug interactions involving hepatic uptake and metabolism.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460209
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Musashino University
• Principal Investigator: Ito Kiyomi 武蔵野大学, 薬学研究所, 教授 (60232435)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 薬物相互作用 / 生理学的薬物速度論モデル

Outline of Final Research Achievements

For drugs metabolized by multiple enzymes, precise estimation of the contribution of each metabolic enzyme is important in evaluating the effects of metabolic inhibition by co-administered drugs. Importance of paying attention to the buffer condition in in vitro metabolic studies was confirmed by our study investigating the contribution of CYP2C8 and CYP3A4 in the metabolism of repaglinide. In addition, a physiologically based pharmacokinetic (PBPK) modeling analysis demonstrated the involvement of both hepatic uptake inhibition and metabolic inhibition in the interaction between clarithromycin and glibenclamide. Similar PBPK analyses as in the present study are expected to facilitate the efficiency in drug development and to provide security in medication involving multiple drugs.

Free Research Field

薬物動態学