| Project/Area Number |
18K14991
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Showa University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
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| Keywords | 13C-呼気試験 / 13C-リドカイン / CYP3A / 薬物代謝評価 / 薬物代謝 / PBPKモデル |
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| Outline of Final Research Achievements |
A novel breath test using 13C-lidocaine was evaluated for developing a rapid and convenient quantitative evaluation method for assessing individual cytochrome P450 (CYP) metabolic activity for use in personalized drug therapy.
Results of breath tests and pharmacokinetic studies in mice with altered drug metabolic activity suggested that the breath test response after oral administration of 13C-lidocaine reflected CYP3A metabolic activity in the first-pass effect. This is consistent with the results of physiologically based pharmacokinetic (PBPK) model analysis. Furthermore, a positive correlation was observed between the respiratory response parameters and midazolam kinetic parameters (a conventional evaluation method of CYP3A activity) .This study demonstrates that the 13C-lidocaine breath test provides a rapid and easy quantitative evaluation of changes in CYP3A metabolic activity.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、13C-リドカイン経口投与呼気試験を用いて、非侵襲的かつ迅速簡便に、その時点での患者の薬物代謝能を定量的に評価できる可能性が示された。この新たな呼気試験法が確立されれば、臨床現場において非侵襲的かつ迅速簡便に患者個々の薬物代謝能を評価することが可能となり、その時点の患者の状態に応じた薬物選択や投与量調節の支援に役立ち、適正な個別化薬物療法に大きく貢献できると考えられる。本研究成果は、その基礎データの構築と従来の評価方法との比較検討を行い、本評価法の確立に重要な情報を構築できたと考える。
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