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Individual dose of tofacitinib based on pharmacokinetic and pharmacogenomic analysis

Research Project

Project/Area Number 26860100
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionShiga University of Medical Science

Principal Investigator

Hira Daiki  滋賀医科大学, 医学部, 特任助教 (50636959)

Research Collaborator TERADA TOMOHIRO  滋賀医科大学, 医学部, 教授 (10324641)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords個別医療 / トファシチニブ / 薬物動態 / 関節リウマチ
Outline of Final Research Achievements

The aim of the present study is to develop the individual dose of tofacitinib, which is a novel synthetic disease modifying anti-rheumatic drug (DMARD) that selectively inhibits Janus kinase (JAKs), particularly JAK1 and JAK3.
In the present study, a novel and simple HPLC-UV assay method for the estimation of tofacinib concentration has been developed and validated. Transport characteristics of ABCB1 (P-glycoprotein, P-gp) and ABCG2 (breast cancer resistance protein, BCRP) were assessed by HEK293 cells stably expressing ABCB1 and ABCG2. The cellular accumulation of tofacitinib in HEK293-ABCB1 and HEK293-ABCG2 were markedly decreased than that in HEK293 cell as a control. These findings suggest that pharmacogenomic analysis help to optimize the individual dose of tofacitinib.

Report

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

    (11 results)

All 2017 2016 2015 2014

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Previous Dosage of Allopurinol Is a Strong Determinant of Febuxostat Efficacy2017

    • Author(s)
      Koide H, Hira D, Tsujimoto M, Katsube Y, Minegaki T, Uzu T, Ikeda Y, Morita SY, Nishiguchi K, Terada T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 5 Pages: 681-686

    • DOI

      10.1248/bpb.b16-00972

    • NAID

      130005631961

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Letter: CYP3A4/5 genotype status and outcome of vonoprazan-containing Helicobacter pylori eradication therapy in Japan.2017

    • Author(s)
      Sugimoto M, Ban H, Hira D, Kamiya T, Otsuka T, Inatomi O, Bamba S, Terada T, Andoh A.
    • Journal Title

      Aliment Pharmacol Ther.

      Volume: 45 Issue: 7 Pages: 1009-1010

    • DOI

      10.1111/apt.13959

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacokinetic analysis of a hemodialyzed patient treated with pazopanib.2016

    • Author(s)
      S. Noda, D. Hira, S. Kageyama, (他6名)
    • Journal Title

      Clinical Genitourinary Cancer

      Volume: 14(4) Issue: 4 Pages: e453-e456

    • DOI

      10.1016/j.clgc.2016.03.016

    • Description
      in press
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intestinal and hepatic drug transporters: pharmacokinetic, pathophysiological, and pharmacogenetic roles.2015

    • Author(s)
      Tomohiro Terada, Daiki Hira.
    • Journal Title

      Journal of Gastroenterology

      Volume: 50 Issue: 5 Pages: 508-519

    • DOI

      10.1007/s00535-015-1061-4

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Population pharmacokinetics and therapeutic efficacy of febuxostat in patients with severe renal impairment.2015

    • Author(s)
      Daiki Hira, Yugo Chisaki, Satoshi Noda, Hisazumi Araki, Takashi Uzu, Hiroshi Maegawa, Yoshitaka Yano, Shin-ya Morita, and Tomohiro Terada.
    • Journal Title

      Pharmacology

      Volume: 96 Issue: 1-2 Pages: 90-98

    • DOI

      10.1159/000434633

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Assessment of Sunitinib-Induced Toxicities and Clinical Outcomes Based on Therapeutic Drug Monitoring of Sunitinib for Patients With Renal Cell Carcinoma. Clin Genitourin Cancer.2015

    • Author(s)
      Noda S, Otsuji T, Baba M, Yoshida T, Kageyama S, Okamoto K, Okada Y, Kawauchi A, Onishi H, Hira D, Morita SY, Terada T
    • Journal Title

      Clinical Genitourinary Cancer

      Volume: in press Issue: 4 Pages: 350-358

    • DOI

      10.1016/j.clgc.2015.01.007

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduction in gastrointestinal toxicity during S-1 monotherapy for patients with gastric cancer by gastric secretion inhibitors.2014

    • Author(s)
      Yugo Chisaki, Satoshi Noda, Daiki Hira, Shin-ya Morita, Yoshitaka Yano, Tomohiro Terada.
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 37 Pages: 1158-1161

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 院内におけるPGx検査の体制構築に向けた取組みについて2016

    • Author(s)
      平 大樹, 寺田智祐
    • Organizer
      第26回日本医療薬学会年会
    • Place of Presentation
      京都
    • Year and Date
      2016-09-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Pharmacometrics in clinical practice: Population PK analysis of febuxostat in patients with severe renal impairment2016

    • Author(s)
      Daiki Hira, Tomohiro Terada
    • Organizer
      The 2nd A3 Pharmcometrics Symposium
    • Place of Presentation
      Daejeon, Republic of Korea
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 経口関節リウマチ分子標的薬の薬物動態影響因子の探索2015

    • Author(s)
      平 大樹, 寺田智祐
    • Organizer
      平成26年度学長裁量経費による研究助成成果発表会
    • Place of Presentation
      滋賀医科大学
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 高度腎機能低下患者におけるフェブキソスタットの薬物動態、治療効果の解析2014

    • Author(s)
      平 大樹, 地嵜悠吾, 野田哲史, 宇津 貴, 前川 聡, 矢野義孝, 森田真也, 寺田智祐
    • Organizer
      医療薬学フォーラム 2014
    • Place of Presentation
      東京
    • Year and Date
      2014-06-28 – 2014-06-29
    • Related Report
      2014 Research-status Report

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

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