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2013 Fiscal Year Final Research Report

Establishment of pharmacogenetic-based dosing algorithm of warfarin for Asian, Caucasian and African American patients

Research Project

  • PDF
Project/Area Number 23590652
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionMeiji Pharmaceutical University

Principal Investigator

TAKAHASHI Harumi  明治薬科大学, 薬学部, 教授 (20211344)

Co-Investigator(Kenkyū-buntansha) SHIOMI Mari  明治薬科大学, 薬学部, 助手 (30300768)
Co-Investigator(Renkei-kenkyūsha) NANJHO Shuji  東邦大学, 医学部, 准教授 (70328615)
SASAKI Yasutuna  埼玉医科大学, 医学部, 教授 (20235279)
FUJITA Kenichi  埼玉医科大学, 医学部, 講師 (60281820)
Research Collaborator LEE T.M. Michael  Institute of Biomedical Sciences, Academia Sinica
CAVALLARI Larisa H  イリノイ大学シカゴ校, 薬学部, 准教授
Project Period (FY) 2011 – 2013
Keywordsワルファリン / 個体差 / 応答性 / CYP2C9 / VKORC1 / 遺伝子多型 / INR
Research Abstract

To establish the initiating dosing algorithm of warfarin in 3 different populations (Asian, African American and Caucasians), pharmacokinetic (PK) and pharmacodynamic (PD) factors associated with inter-individual variability in anti-coagulation responses were investigated by performing the retrospective and prospective clinical studies.
Multivariate analyses showed that mutations of CYP2C9*8,CYP2C9*3,CYP2C9*2, sex and age were predictors of PK (clearance) and that mutations of VKORC1*2 & CYP4F2*3 and the baseline coagulation activity were predictors of PD (IC50 & the non-linear index). Furthermore, all results indicate that factors associated with the reduced metabolic activity of warfarin might be critical determinants of the over-anticoagulation response during initiation therapy in Asian patients.

  • Research Products

    (13 results)

All 2013 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (6 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Genetic variants associated with warfarin dose in African-American individuals : a genome-wide association study2013

    • Author(s)
      Perera MA, Cavallari LH, Limdi NA, Gamazon ER, Konkashbaev A, Daneshjou R, Pluzhnikov A, Crawford DC, Wang J, Liu N, Tatonetti N, Bourgeois S, Takahashi H, Bradford Y, Burkley BM, Desnick RJ, Halperin JL, Khalifa SI, Langaee TY, Lubitz SA, Nutescu EA, Oetjens M, Shahin MH, Patel SR, Sagreiya H, Tector M, Weck KE, Rieder MJ, Scott SA, Wu AHB, Burmester JK, Wadelius M, Deloukas P, Wagner MJ, Mushiroda T, Kubo M, Roden DM, Cox NJ, Altman RB, Klein TE, Nakamura Y, Johnson JA
    • Journal Title

      Lancet

      Volume: 382 Pages: 790-796

    • DOI

      10.1016/S0140-6736(13)60681-9

    • Peer Reviewed
  • [Journal Article] CYP2C9 promoter region SNPs linked to the R150H polymorphism are functional suggesting their role in CYP2C9*8-mediated effects2013

    • Author(s)
      Larisa H. Cavallari, David Vaynshteyn, Kimberly M. Freeman, Danxin Wang, Minoli A. Perera, Harumi Takahashi, Katarzyna Drozda, Shitalben R. Patel, Hyun-Young Jeong
    • Journal Title

      Pharmacogenet. Genomics

      Volume: 23(4) Pages: 228-231

    • DOI

      10.1097/FPC.0b013e32835e95c7

    • Peer Reviewed
  • [Journal Article] Inter- individual differences in baseline coagulation activities and their implications for INR control during warfarin initiation therapy, Clin2012

    • Author(s)
      Yosuke Ichimura, Harumi Takahashi, Michael TM Lee, Mari Shiomi, Kiyoshi Mihara, Takashi Morita, Chen, Hirotoshi Echizen
    • Journal Title

      Pharmacokinet

      Volume: 51(12) Pages: 799-808

    • DOI

      10.1038/clpt.2011.269

    • Peer Reviewed
  • [Journal Article] Decreased warfarin clearance associated with the CYP2C9 R150H(*8) polymorphism2012

    • Author(s)
      Yong Liu, Hyun-Young Jeong, Harumi Takahashi, Katarzyna Drozda, Shitalben R. Patel, Nancy L. Shapiro, Edith A. Nutescu, Larisa H. Cavallari
    • Journal Title

      Clin. Pharmacol. Ther

      Volume: 91 Pages: 660-665

    • DOI

      10.1007/s40262-012-0009-6

    • Peer Reviewed
  • [Presentation] 抗凝固薬ワルファリンの母集団薬物動態/薬力学モデル解析2013

    • Author(s)
      大原みなみ, MTM Lee, 長井塁, 小野塚秋子, 有馬亜希, YT Chen, 高橋晴美
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      20130300
  • [Presentation] Warfarinと抗癌薬の相互作用に関するin vitroからin vivoへの予測2013

    • Author(s)
      岡澤司, 大原みなみ, 平出誠, 魚住真哉, 上村有美, 中山卓, 高橋晴美
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      20130300
  • [Presentation] 抗凝固薬の個別化治療:ゲノム情報の臨床的意義2011

    • Author(s)
      高橋晴美
    • Organizer
      第32回日本臨床薬理学会年会シンポジウム
    • Place of Presentation
      浜松
    • Year and Date
      20111200
  • [Presentation] Association between the CYP2C9*8 variant and warfarin clearance in African Americans2011

    • Author(s)
      Katarzyna Drozda, Harumi Takahashi, Shitalben R Patel, Nancy L Shapiro, Edith A Nutescu, Larisa H Cavallari
    • Organizer
      2011 Annual Meeting of American College of Clinical Pharmacy
    • Place of Presentation
      IL,USA
    • Year and Date
      20111016-19
  • [Presentation] Inter-individual differences in baseline coagulation activities and their clinical implications for warfarin therapy2011

    • Author(s)
      Harumi Takahashi, Yosuke Ichimura, M.T. Michael Lee, Mari Shiomi, Kiyoshi Mihara, Takashi Morita, Yuan-Tsong Chen, Hirotoshi Echizen
    • Organizer
      The 23^<rd> Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Kyoto
    • Year and Date
      20110723-19
  • [Presentation] Prediction of warfarin exposure and INR response in children2011

    • Author(s)
      A-K Hamberg, M Wadelius, H Takahashi, L Friberg, EN Jonsson
    • Organizer
      The PAGE (the Population Approach Group in Europe) meeting
    • Place of Presentation
      Athens, Greece
    • Year and Date
      20110607-10
  • [Book] 本態性高血圧症, 慢性心不全, 冠攣縮性狭心症, 消化性潰瘍, 脂質異常症, 再生不良性貧血, 2ページで理解する標準薬物治療ファイル2013

    • Author(s)
      高橋晴美 (日本アプライド・セラピューティクス学会編)
    • Total Pages
      2-3, 4-5, 12-13, 28-29, 44-45, 52-53
    • Publisher
      南山堂
  • [Book] III.心臓・血管系疾患/腎疾患/泌尿・生殖器疾患虚血性心疾患, 薬物治療スキルアップシリーズ医療薬学テキスト2011

    • Author(s)
      川名純一, 小海春恵, 高橋晴美 (北田光一編集総括)
    • Total Pages
      48-63
    • Publisher
      南江堂
  • [Remarks]

    • URL

      http://www.my-pharm.ac.jp/~yakuzai

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Published: 2015-07-16  

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