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Development of a system, which can pre-avoid anti-platelet agents-induced severe hepatic disfunction that is difficult to predict

Research Project

Project/Area Number 20390045
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionChiba University

Principal Investigator

ARIYOSHI Noritaka  千葉大学, 医学部附属病院, 准教授 (00243957)

Co-Investigator(Kenkyū-buntansha) KITADA Mitsukazu  千葉大学, 医学部附属病院, 教授 (90110345)
Co-Investigator(Renkei-kenkyūsha) ISHII Itsuko  千葉大学, 大学院・薬学研究院, 准教授 (00202929)
Project Period (FY) 2008 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywordsオーダーメイド医療 / チェノピリジン / 重篤肝障害 / Idiosyncratic / HLA allele / 簡易遺伝子診断 / 臨床研究 / オーダーメード医療 / 薬物誘発性肝障害 / HLAハプロタイプ / 遺伝子診断 / チエノピリジン / チエノピリじン / HLA ハプロタイプ
Research Abstract

We have developed a simple genotyping method to detect HLA-A^*3303, which appeared to be responsible for severe hepatic disfunction induced by ticlopidine. In this study, we have confirmed that another candidate gene polymorphism, which may be involved in ticlopidine-induced hepatotoxicity. We found that either or both HLA-A^*0206 and HLA-B^*3901 may be responsible for clopidogrel-induced hepatic disfunction in our preliminary studies. Thus, simple genotyping methods to detect these specific HLA alleles were developed. Then, we applied these genotyping methods to confirm whether either or both HLA alleles were truly related to the clopidogrel-induced hepatic disfunction in the second population. However, reproducible results were not obtained, possibly due to a small number of patients with clopidogrel-induced hepatic disfunction. It was suggested that different genetic factors may be involved in hepatic disfunction induced by ticlopidine and clopidogrel, although we have not identify the causal HLA allele responsible for clopidogrel-induced hepatic disfunction. These results indicate that ticlopidine and clopidogrel could be used safely as alternative drug each other.

Report

(6 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report   Self-evaluation Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (13 results)

All 2011 2010 2009 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (8 results) Remarks (1 results)

  • [Journal Article] Enhanced susceptibility of HLA-mediated ticlo-pidine-induced idiosyncratic hepato-toxicity by CYP2B6 polymorphism in Japanese2010

    • Author(s)
      Ariyoshi N, Iga Y, Hirata K, Sato Y, Miura G, Ishii I, Nagamori S, Kitada M.
    • Journal Title

      Drug Metab Pharmacokinet

      Volume: 25(3) Pages: 298-306

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced susceptibility of HLA-mediated ticlopidine-induced idiosyncratic hepatotoxicity by CYP2B6 polymorphism in Japanese.2010

    • Author(s)
      Ariyoshi N, Iga Y, Hirata K, Sato Y, Miura G, Ishii I, Nagamori S, Kitada M.
    • Journal Title

      Drug Metab Pharmacokinet. 25

      Pages: 298-306

    • NAID

      10027583017

    • Related Report
      2010 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Enhanced susceptibility of HLA-mediated ticlopidine-induced idiosyncratic hepatotoxicity by CYP2B6 polymorphism in Japanese2010

    • Author(s)
      Ariyoshi N, etal.
    • Journal Title

      Drug Metab.Pharmacokine

      Volume: 25 Pages: 298-306

    • NAID

      10027583017

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced susceptibility of HLA-mediated ticlopidine-induced idiosyncratic hepatotoxicity by CYP2B6 polymorphism in Japanese2010

    • Author(s)
      Ariyoshi N, et al.
    • Journal Title

      Drug Metab. Pharmacokinet 25(In press)

    • NAID

      10027583017

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] チエノピリジン誘発肝障害の感受性に関わる遺伝的素因の検討2011

    • Author(s)
      有吉範高, 内山数貴
    • Organizer
      第21回日本医療薬学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2011-10-01
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 抗血小板薬誘発肝障害との関連性が疑われるHLA型遺伝子診断法の開発2011

    • Author(s)
      内山数貴, 有吉範高ら
    • Organizer
      第131回日本薬学会年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-30
    • Related Report
      2011 Final Research Report 2010 Self-evaluation Report
  • [Presentation] 抗血小板薬誘発肝障害との関連性が疑われるHLA型遺伝子診断法の開発2011

    • Author(s)
      内山数貴、有吉範高, ほか
    • Organizer
      第131回日本薬学会年会
    • Place of Presentation
      静岡(震災の影響で年会中止なるも発表成立)
    • Year and Date
      2011-03-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] 医療機関向けに開発したHLA-A^*3303簡便・迅速遺伝子診断法の改良2009

    • Author(s)
      有吉範高, 久保田史佳ら
    • Organizer
      第19回日本医療薬学会年会
    • Place of Presentation
      長崎
    • Year and Date
      2009-10-25
    • Related Report
      2011 Final Research Report
  • [Presentation] 医療機関向けに開発したHLA-A*3303簡便・迅速遺伝子診断法の改良2009

    • Author(s)
      有吉範高、久保田史佳, ら
    • Organizer
      第19回日本医療薬学会年会
    • Place of Presentation
      長崎
    • Year and Date
      2009-10-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] 医療機関向けに開発したHLA-A^*3303簡便・迅速遺伝子診断法の改良.2009

    • Author(s)
      有吉範高、久保田史佳
    • Organizer
      第19回日本医療薬学会年会
    • Place of Presentation
      長崎
    • Year and Date
      2009-10-24
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] 特定HLA-Aハプロタイピングの簡易診断法の開発と評価2009

    • Author(s)
      久保田史佳, 有吉範高ら
    • Organizer
      第129回日本薬学会年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-26
    • Related Report
      2011 Final Research Report 2010 Self-evaluation Report
  • [Presentation] 特定HLA-Aハプロタイピングの簡易診断法の開発と評価2009

    • Author(s)
      久保田史佳ら
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-26
    • Related Report
      2008 Annual Research Report
  • [Remarks] 学会発表(3)は、全演題の5%にあたるハイライト演題に選出された。

    • Related Report
      2010 Self-evaluation Report

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Published: 2008-04-01   Modified: 2016-04-21  

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