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Change in the PK profile of metabolites by inhibition of metabolic enzyme: elucidation of mechanism and establishment of predictive method

Research Project

Project/Area Number 25870941
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Drug development chemistry
Research InstitutionSetsunan University

Principal Investigator

KATAOKA Makoto  摂南大学, 薬学部, 講師 (00340860)

Research Collaborator HASEGAWA Tsubasa  摂南大学大学院, 薬学研究科
NAKANISHI Satomi  摂南大学, 薬学部
HATAYAMA Syo  摂南大学, 薬学部
ONO Yasuaki  摂南大学, 薬学部
UEDA Akihiro  摂南大学, 薬学部
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords薬物相互作用 / CYP3A4 / 代謝物 / CYP阻害 / CYP3A / 薬物間相互作用 / 代謝物毒性
Outline of Final Research Achievements

In order to predict the change in the PK profile of metabolites in DDI induced humans, PK profiles of parent drugs and metabolites in rats and monkeys were investigated. It was found that the systemic exposure of not only parent drugs but also their metabolites was significantly increased by DDI. Furthermore, this phenomenon was also observed in monkeys in which systemic clearance is comparable to that in humans. These findings indicated that significant increase of systemic exposure of metabolites by DDI could observe in humans. Metabolic activity and the change in it by DDI in the part of metabolic organ are important to determine the PK profile of metabolites. The mathematical modeling has been made to simulate our finding phenomenon, which can be useful to understand and predict the change in the PK profile of metabolites by DDI.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (6 results)

All 2015 2014 Other

All Presentation (6 results)

  • [Presentation] DDI による医薬品代謝物の体内動態の変動: カニクイザルを用いた検討2015

    • Author(s)
      小野泰明、長谷川翼、本田昌平、東野晴輝、片岡誠、設楽悦久、山下伸二
    • Organizer
      日本薬剤学会第30年会
    • Place of Presentation
      長崎
    • Year and Date
      2015-05-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] DDI による医薬品代謝物の体内動態の変動:PBPK モデル解析2015

    • Author(s)
      長谷川翼、小野泰明、本田昌平、東野晴輝、片岡誠、設楽悦久、山下伸二
    • Organizer
      日本薬剤学会第30年会
    • Place of Presentation
      長崎
    • Year and Date
      2015-05-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Kinetic Analysis on the Fluctuation of Systemic Exposure of Drug metabolites Caused by DDI2014

    • Author(s)
      Hasegawa T, Nakanishi S, Higashino H, Kataoka M, Yamashita S
    • Organizer
      2014 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition
    • Place of Presentation
      San Diego
    • Year and Date
      2014-11-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 薬物間相互作用による代謝物の血中曝露量の変動(2):in vitro での検証2014

    • Author(s)
      中西佐都美、長谷川翼、東野晴輝、政岡祥江、片岡誠、佐久間信至、山下伸二
    • Organizer
      日本薬剤学会第29年会
    • Place of Presentation
      大宮
    • Year and Date
      2014-05-22 – 2015-05-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 薬物間相互作用による代謝物の血中曝露量の変動(1) : 速度論的解析2014

    • Author(s)
      長谷川翼、中西佐都美、畑山翔、東野晴輝、政岡祥江、片岡誠、佐久間信至、山下伸二
    • Organizer
      日本薬剤学会第29年会
    • Place of Presentation
      大宮
    • Year and Date
      2014-05-20 – 2014-05-22
    • Related Report
      2014 Annual Research Report 2013 Research-status Report
  • [Presentation] 薬物間相互作用による代謝物の血中暴露量の変動(2):in vitroでの検証

    • Author(s)
      中西佐都美、長谷川翼、東野晴輝、政岡祥江、片岡誠、佐久間信至、山下伸二
    • Organizer
      日本薬剤学会第29年会
    • Place of Presentation
      大宮
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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