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Quantitative prediction of bioavailability and drug-drug interactions of orally administered drugs

Research Project

Project/Area Number 26460204
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionKitasato University

Principal Investigator

ITOH Tomoo  北里大学, 薬学部, 教授 (30223168)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords経口投与 / バイオアベイラビリティ / 薬物相互作用 / 定量的予測 / 相互作用 / CYP3A4
Outline of Final Research Achievements

The present study aimed to improve a model to quantitatively predict the bioavailability and drug-drug interactions for orally administered CYP3A substrates. Alprazolam (ALP), midazolam (MDZ) and triazolam (TRZ) were used as CYP3A substrates, and ritonavir (RIT) and erythromycin (ERY) were used as CYP3A inhibitors. Metabolic and inhibition parameters of those drugs were obtained in in vitro studies. Transfer parameters in the intestinal epithelial cells were also estimated in vitro using Caco-2 cells. The obtained parameters were incorporated into an ITAM-PK model to predict the oral bioavailability of ALP, MDZ and TRZ, and also interactions between CYP3A substrates and CYP3A inhibitors.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015 2014

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (5 results)

  • [Journal Article] Prediction of drug-induced liver injury using keratinocytes.2017

    • Author(s)
      Hirashima R, Itoh T, Tukey RH, Fujiwara R.
    • Journal Title

      J Appl Toxicol.

      Volume: 印刷中 Issue: 7 Pages: 863-872

    • DOI

      10.1002/jat.3435

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA expression in the vildagliptin-treated two- and three-dimensional HepG2 cells.2016

    • Author(s)
      Yamashita Y, Asakura M, Mitsugi R, Fujii H, Nagai K, Atsuda K, Itoh T, Fujiwara R.
    • Journal Title

      Drug Metab Pharmacokinet.

      Volume: 31(3) Issue: 3 Pages: 201-9

    • DOI

      10.1016/j.dmpk.2016.02.004

    • NAID

      50014431262

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity.2016

    • Author(s)
      Hirashima R, Michimae H, Takemoto H, Sasaki A, Kobayashi Y, Itoh T, Tukey RH, Fujiwara R.
    • Journal Title

      Mol Pharmacol.

      Volume: 90(3) Issue: 3 Pages: 265-74

    • DOI

      10.1124/mol.116.104174

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Underlying mechanism of drug-drug interaction between pioglitazone and gemfibrozil: Gemfibrozil acyl-glucuronide is a mechanism-based inhibitor of CYP2C8.2015

    • Author(s)
      Takagi M, Sakamoto M, Itoh T, Fujiwara R.
    • Journal Title

      Drug Metab. Pharmacokinet.

      Volume: 30 Issue: 4 Pages: 288-94

    • DOI

      10.1016/j.dmpk.2015.05.001

    • NAID

      210000180871

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nicotine regulates the expression of UDP-glucuronosyltransferase (UGT) in humanized UGT1 mouse brain.2015

    • Author(s)
      Sakamoto M, Itoh T, Tukey RH, Fujiwara R.
    • Journal Title

      Drug Metab. Pharmacokinet.

      Volume: 30 Issue: 4 Pages: 269-75

    • DOI

      10.1016/j.dmpk.2015.04.004

    • NAID

      50014429962

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dipeptidyl peptidase-4 greatly contributes to the hydrolysis of vildagliptin in human liver.2015

    • Author(s)
      Asakura M, Fujii H, Atsuda K, Itoh T, Fujiwara R.
    • Journal Title

      Drug Metab. Dispos.

      Volume: 43 Issue: 4 Pages: 477-84

    • DOI

      10.1124/dmd.114.062331

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extensive protein-protein interactions involving cytochrome P450 3A4: a poosible contributor the fromation of metabolosome.2014

    • Author(s)
      Fujiwara R and Itoh T.
    • Journal Title

      Pharmacol Res Perspect.

      Volume: 2 Issue: 5 Pages: 1-5

    • DOI

      10.1002/prp2.53

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 免疫抑制剤による皮膚発がん誘導メカニズムの解明2017

    • Author(s)
      平島梨夏、田中優史、藤原亮一、伊藤智夫
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      宮城県仙台市
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヘムオキシゲナーゼ-1(HO-1)阻害剤を用いたCrigler-Najjar症候群Ⅰ型の致死性回避2017

    • Author(s)
      植村明日香、三ツ木諒、藤原亮一、伊藤智夫
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      宮城県仙台市
    • Related Report
      2016 Annual Research Report
  • [Presentation] 2型糖尿病治療薬ビルダグリプチンによるS100A8/A9の発現誘導2016

    • Author(s)
      朝倉充俊、藤原亮一、藤井秀明、厚田幸一郎、伊藤智夫
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] HepG2細胞におけるmiR-877の機能解析2016

    • Author(s)
      三ツ木諒、藤原亮一、伊藤智夫
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 肝細胞の三次元培養技術を応用したビルダグリプチン誘導性マイクロRNA発現誘導解析2016

    • Author(s)
      山下康也、朝倉充俊、藤原亮一、藤井秀明、厚田幸一郎、伊藤智夫
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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