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2011 Fiscal Year Final Research Report

Mechanism of drug resistance and its rational treatment based on pharmacodynamic analysis.

Research Project

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Project/Area Number 21590150
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

YAMAMOTO Kojiro  群馬大学, 大学院・医学系研究科, 教授 (70174787)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Tomonori  群馬大学, 大学院・医学系研究科, 准教授 (30251151)
NAKAMURA Katsunori  信州大学, 医学部附属病院, 准教授 (20361363)
Project Period (FY) 2009 – 2011
Keywords薬剤抵抗性 / ワルファリン / ビタミンK / VKORC1 / アザチオプリン / ITPA
Research Abstract

Vitamin K oxide reductase gene VKORC1 was important as a warfarin-resistant factor, while influence of CYP4F2, a vitamin K metabolism enzyme, was limited. Effect of thiopurine methyltransferase (TPMT) and inosine triphosphorus pyrophosphohydrolase (ITPA) was investigated in the systemic lupus erythematosus patients. Since treatment with azathioprine was provided at a low dose traditionally in Japan, azathioprine therapy is effective in the patients who had ITPA gene variant.

  • Research Products

    (21 results)

All 2011 2010 2009 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results) Presentation (13 results) Remarks (1 results)

  • [Journal Article] CYP4F2 gene polymorphism as a contributor to warfar in maintenance dose in Japanese subjects2011

    • Author(s)
      Nakamura K, Obayashi K, Araki T, Aomori T, Fujita Y, Okada Y, Kurabayashi M, Hasegawa A, Ohmori S, Nakamura T, Yamamoto K
    • Journal Title

      J. Pharmacy Ther

      Volume: (In press)

    • Peer Reviewed
  • [Journal Article] Influence of CYP2C9 and VKORC1 polymorphisms on time to determine the warfarin maintenance dose2011

    • Author(s)
      Aomori T, Obayashi K, Fujita Y, Araki T, Nakamura K, Nakamura T, Kurabayashi M, Yamamoto K
    • Journal Title

      Pharmazie

      Volume: 66 Pages: 222-225

    • Peer Reviewed
  • [Journal Article] Inosine triphosphate pyrophosphatase 94C>A polymorphism : clinical implications for patients with systemic lupus erythematosus treated with azathioprine2010

    • Author(s)
      Yamamoto K, Okada Y, Nakamura K, Hiromura K, Nojima Y, Nakamura T
    • Journal Title

      Exp Opin Drug Saf

      Volume: 9(3) Pages: 447-57

    • Peer Reviewed
  • [Journal Article] Rapid SNP detection of the cytochrome P450 (CYP) 2C9 and the vitamin K oxide reductase (VKOR) gene for the warfarin dose adjustment by SMart-Amplification Process2009

    • Author(s)
      Aomori T, Yamamoto K, Oguchi-Katayama A, Kawai Y, Ishidao T, Mitani Y, Kogo Y, Lezhava A, Fujita Y, Obayashi K, Nakamura K, Kohnke H, Wadelius M, Ekstrom L, Skogastierna C, Rane A, Kurabayashi M, Murakami M, Cizdziel PE., Hayashizaki Y, Horiuchi R
    • Journal Title

      Clin. Chem

      Volume: 55(4) Pages: 804-12

    • Peer Reviewed
  • [Journal Article] Pro32Thr polymorphism of inosine triphosphate gene predicts efficacy of low-dose azathioprine for patients with systemic lupus erythematosus2009

    • Author(s)
      Okada Y, Nakamura K, Hiromura K, Nojima K, Horiuchi R, Yamamoto K
    • Journal Title

      Clin. Pharmacol. Ther

      Volume: 85(5) Pages: 527-30

    • Peer Reviewed
  • [Journal Article] 山本康次郎, 岡田裕子, 中村智徳2009

    • Author(s)
      山本康次郎, 岡田裕子, 中村智徳
    • Journal Title

      医薬ジャーナル

      Volume: 45(12) Pages: 3089-94

  • [Journal Article] Sensitive and simple determination of vitamin K1 in human plasma by ultra-performance liquid chromatography coupled with a fluorescence detector

    • Author(s)
      Ohno, I, Araki T, Kawano M, Nakamura T, Yamamoto K
    • Journal Title

      J Liq Chromatogr & Related Tech.

      Volume: (in press)

    • Peer Reviewed
  • [Presentation] Association of genotype, pharmacokinetics of vitamin Ks, and response of warfarin2011

    • Author(s)
      Takuya Araki, Masashi Kawano, Izumi Ohno, Tomonori Nakamura, Koujirou Yamamoto
    • Organizer
      第5回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      名古屋大学病院
    • Year and Date
      20111126-27
  • [Presentation] Effect of genetic polymorphisms on the efficacy of low-dose azathioprine therapy in patients with systemic lupus erythematosus2011

    • Author(s)
      Aomori T, Nagamine A, Takenaka M, Okada Y, Hiromura K, Nojima Y, Araki T, Nakamura T, Yamamoto K
    • Organizer
      10th Congress of the European Association for Clinical Pharmacology and Therapeutics
    • Place of Presentation
      Budapest, Hungary
    • Year and Date
      20110626-29
  • [Presentation] Comparison of the VKOR inhibitory activity by S-and R-warfarin2011

    • Author(s)
      Kawano M, Araki T, Nakamura T, Yamamoto K
    • Organizer
      2nd Asian Federation for Pharmaceutical Sciences
    • Place of Presentation
      Kuala Lumpur, Malaysia
    • Year and Date
      2011-12-09
  • [Presentation] 肝ミクロソームを用いたSおよびRワルファリンによるVKOR阻害活性の比較検討2011

    • Author(s)
      川野雅嗣, 荒木拓也, 中村智徳, 山本康次郎
    • Organizer
      第55回日本薬学会関東支部大会
    • Place of Presentation
      東邦大学、船橋
    • Year and Date
      2011-10-08
  • [Presentation] Contribution of genetic polymorphisms to the efficacy of low-dose azathioprine therapy in Japanese patients with systemic lupus erythematosus2010

    • Author(s)
      Ayumu Nagamine, Miki Takenaka, Tohru Aomori, Yuko Okada, Keiju Hiromura, Yoshihisa Nojima, Takuya Araki, Tomonori Nakamura, Koujirou Yamamoto
    • Organizer
      第4回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      20101127-28
  • [Presentation] The Contribution of CYP3A5 and MDR1 (ABCB1) Polymorphisms on the pharmacokinetics of tacrolimus in patients with Rheumatoid arthritis and Lupus nephritis2010

    • Author(s)
      Ayano Ito, Yuko Okada, Keiju Hiromura, Yoshihisa Nojima, Takuya Araki, Tomonori Nakamura, Koujirou Yamamoto
    • Organizer
      第4回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      20101127-28
  • [Presentation] ITPA遺伝子多型解析のSLE患者におけるアザチオプリン薬物療法への応用. シンポジウム20 病院薬剤師による薬物治療個別化への遺伝子情報の活用2010

    • Author(s)
      中村智徳
    • Organizer
      第20回日本医療薬学会年会
    • Place of Presentation
      千葉
    • Year and Date
      20101113-14
  • [Presentation] ワルファリン維持投与量に対するCYP4F2遺伝子多型の影響の検討2010

    • Author(s)
      中村克徳, 荒木拓也, 大林恭子, 川名純一, 倉林正彦, 中村智徳, 大森栄, 山本康次郎
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Year and Date
      20100328-30
  • [Presentation] Individualization of Azathioprine dose for patients with Systemic Lupus Erythematosus 38th European Society of Clinical Pharmacy2009

    • Author(s)
      Koujirou Yamamoto, Yuko Okada, Katsunori Nakamura, Tomonori Nakamura, Keiju Hiromura, Yoshihisa Nojima
    • Place of Presentation
      Geneva, Switzerland
    • Year and Date
      20091103-06
  • [Presentation] Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in patients with rheumatoid arthritis and lupus nephritis2009

    • Author(s)
      Tomonori Nakamura, Yuko Okada, Keiju Hiromura, Yoshihisa Nojima, Katsunori Nakamura, Koujirou Yamamoto
    • Organizer
      30th American College of Clinical Pharmacy
    • Place of Presentation
      Anaheim, CA, USA
    • Year and Date
      20091018-21
  • [Presentation] ワルファリン維持投与量決定までの期間に対する VKOR および CYP2C9 遺伝子型の影響2009

    • Author(s)
      青森達, 大林恭子, 中村克徳, 中村智徳, 倉林正彦, 三谷康正, 石田尾武文, 片山敦子, Alexander Lezhava, 林崎良英, 山本康次郎
    • Organizer
      第16回日本遺伝子診療学会
    • Place of Presentation
      札幌
    • Year and Date
      20090730-0801
  • [Presentation] CYP4F2 gene polymorphism as a contributor of warfarin dose in Japanese2009

    • Author(s)
      Katsunori Nakamura, Kyoko Obayashi, Junichi Kawana, Hiroyasu Ogata, Kazuhiko Hanada, Masahiko Kurabayashi, Akira Hasegawa, Tomonori Nakamura, Koujirou Yamamoto
    • Organizer
      16th International Conference on Cytochrome P450
    • Place of Presentation
      Nago, Okinawa, Japan
    • Year and Date
      2009-06-21
  • [Presentation] Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in patients with rheumatoid arthritis and lupus nephritis2009

    • Author(s)
      Tomonori Nakamura, Yuko Okada, Keiju Hiromura, Yoshihisa Nojima, Katsunori Nakamura, Koujirou Yamamoto
    • Organizer
      3rd Asian Pacific Region ISSX Meeting
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2009-05-11
  • [Remarks]

    • URL

      http://clinpharmacol.dept.med.gunma-u.ac.jp/

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Published: 2013-07-31  

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