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Development of the strategic pharmacotherapy using the genetic polymorphisms and the pharmacokinetics in the rheumatoid arthritis

Research Project

Project/Area Number 25460192
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionGifu Pharmaceutical University (2014-2015)
University of Shizuoka (2013)

Principal Investigator

Hayashi Hideki  岐阜薬科大学, 薬学部, 准教授 (00419665)

Co-Investigator(Kenkyū-buntansha) TODOROKI Kenichiro  静岡県立大学, 薬学部, 准教授 (70341451)
YAMADA Hiroshi  静岡県立大学, 薬学部, 教授 (40265252)
ITOH Kunihiko  静岡県立大学, 薬学部, 教授 (90221770)
Research Collaborator TAZOE Yui  静岡県立大学, 大学院, 大学院生
TSUBOI Seiji  JA静岡厚生病院, 副院長
MATSUYAMA Taiji  JA静岡厚生病院, 薬局長
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords関節リウマチ / メトトレキサート / 個別化医療 / 遺伝子解析 / 葉酸トランスポーター / TDM / 臨床薬理 / 血中薬物濃度 / 生物学的製剤 / トランスポーター
Outline of Final Research Achievements

Responsiveness to methotrexate (MTX), the "anchor drug" for treating rheumatoid arthritis (RA), varies among individual patients. In this study we investigated the effects of folate transporter gene expression levels on disease activity in the Japanese patients with RA who were undergoing MTX therapy. The mRNA expression levels of reduced folate carrier 1 (RFC1) in PBMCs from these patients were determined. There were large individual differences in RFC1 mRNA expression levels in both RA patients. RFC1 mRNA expression levels and RA disease activity scores were significantly negatively correlated, as disease activity scores were lower for patients with higher RFC1 mRNA expression levels. Thus, the clinical efficacy of MTX for Japanese RA patients was associated with the expression level of a folate transporter gene. We also attempted the therapeutic drug monitoring using measurement of the biological preparation in plasma and methotrexate and its active metabolite in red blood cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (3 results)

All 2015 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (2 results)

  • [Journal Article] Reduced folate carrier 1 gene expression levels are correlated with methotrexate efficacy in Japanese patients with rheumatoid arthritis.2015

    • Author(s)
      Tazoe Y, Hayashi H, Tsuboi S, Shioura T, Matsuyama T, Yamada H, Hirai K, Tsuji D, Inoue K, Sugiyama T, Itoh K
    • Journal Title

      Drug Metab. Pharmacokinet.

      Volume: in press Issue: 3 Pages: 227-230

    • DOI

      10.1016/j.dmpk.2015.02.001

    • NAID

      50014429955

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 薬物動態インフォメーションを活用した臨床薬理研究の動向と新展開 関節リウマチ治療薬メトトレキサートの薬効に影響する葉酸トランスポーターの遺伝子多型2015

    • Author(s)
      林秀樹, 田添唯, 坪井声示, 松山耐至, 杉山正, 伊藤邦彦
    • Organizer
      日本薬物動態学会第30回年会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 抗体医薬のTDM ―関節リウマチ患者における検討―2014

    • Author(s)
      大鹿雄美,山宮 翔,田添 唯,林 秀樹,松山耐至,坪井声示,轟木堅一郎,井上和幸,辻 大樹,山田 浩,豊岡利正,伊藤邦彦
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本県熊本市
    • Related Report
      2013 Research-status Report

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

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