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Development of a method of serum dabigatran concentration assay using anti-dabigatran monoclonal antibody

Research Project

Project/Area Number 24659355
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionNagasaki International University

Principal Investigator

OISO Shigeru  長崎国際大学, 薬学部, 准教授 (40513106)

Co-Investigator(Kenkyū-buntansha) KARIYAZONO Hiroko  長崎国際大学大学院, 薬学研究科, 教授 (20437958)
MORINAGA Osamu  長崎国際大学大学院, 薬学研究科, 准教授 (60465771)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsダビガトラン / モノクローナル抗体 / ELISA / 血中濃度 / リンゲル液 / 交差反応性 / 血中濃度測定 / 抗体作製
Outline of Final Research Achievements

Dabigatran (DT) is a direct thrombin inhibitor used for the prevention of venous and arterial thromboembolism. DT produces an increased incidence of bleeding in patients with renal dysfunction. Circulating levels of DT are increased in such patients because it is mainly eliminated by renal excretion. To measure DT concentration, we developed a novel enzyme-linked immunosorbent assay (ELISA) using an anti-DT monoclonal antibody (DT-mAb) which was generated by immunization of mice with a DT-keyhole limpet hemocyanin conjugate. The measurement range of dabigatran in competitive ELISA using DT-mAb was 7.8-125 ng/mL. The ELISA signal was not linear using DT-spiked serum in the concentration range of 7.8-125 ng/mL, but was linear when serum ultrafiltrate was used. These results suggested that this competitive ELISA may provide an analysis tool for the determination of free DT in serum ultrafiltrate during therapeutic drug monitoring and pharmacokinetic studies.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (6 results)

All 2015 2014 2013

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results)

  • [Journal Article] Generation of an anti-dabigatran monoclonal antibody and its employment in a highly sensitive and specific enzyme-linked immunosorbent assay for serum dabigatran.2015

    • Author(s)
      Oiso S, Morinaga O, Goroku T, Uto T, Shoyama Y, Kariyazono H.
    • Journal Title

      Therapeutic Drug Monitoring

      Volume: in press Issue: 5 Pages: 594-599

    • DOI

      10.1097/ftd.0000000000000184

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] ダビガトラン血中濃度測定を目指したELISAの開発2014

    • Author(s)
      大磯 茂、森永 紀、宇都 拓洋、正山 征洋、仮屋薗 博子
    • Organizer
      第76回九州山口薬学大会
    • Place of Presentation
      長崎市
    • Year and Date
      2014-11-23 – 2014-11-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗ダビガトランモノクローナル抗体の交差反応性の検討2014

    • Author(s)
      合六 貴昭
    • Organizer
      日本薬学会第134回年会
    • Place of Presentation
      熊本市立体育館
    • Related Report
      2013 Research-status Report
  • [Presentation] ダビガトラン血中濃度測定を目指したELISAの開発2013

    • Author(s)
      大磯 茂
    • Organizer
      第23回日本医療薬学会年会
    • Place of Presentation
      東北大学
    • Related Report
      2013 Research-status Report
  • [Presentation] 特異的モノクローナル抗体を用いたダビガトラン濃度測定法の検討2013

    • Author(s)
      大磯 茂
    • Organizer
      第30回日本薬学会九州支部大会
    • Place of Presentation
      長崎国際大学
    • Related Report
      2013 Research-status Report
  • [Presentation] 抗ダビガトランモノクローナル抗体を用いたダビガトランELISA法の開発2013

    • Author(s)
      大磯 茂、森永 紀、正山 征洋、仮屋薗 博子
    • Organizer
      日本薬学会第133回年会(横浜)
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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