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Development of a novel experimental evaluation method for predicting the drug delivery to the brain in human

Research Project

Project/Area Number 25460199
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionTeikyo University

Principal Investigator

DEGUCHI YOSHIHARU  帝京大学, 薬学部, 教授 (40254255)

Co-Investigator(Kenkyū-buntansha) OKURA TAKASHI  帝京大学, 薬学部, 准教授 (80326123)
HIGUCHI KEI  帝京大学, 薬学部, 助教 (10625304)
Co-Investigator(Renkei-kenkyūsha) HOSOYAMADA MAKOTO  帝京大学, 薬学部, 教授 (00291659)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords血液脳関門 / ヒト脳移行性 / トランスポーター / 有機カチオン性薬物 / ヒト血液脳関門モデル細胞 / 循環培養システム / フロー培養システム / 血液脳関門モデル細胞
Outline of Final Research Achievements

The objectives of this study are to develop reliable experimental-method(s) for predicting functions of human blood-brain barrier (BBB), using hCMEC/D3 cells, an in vitro human BBB model. As for the research achievements, 1) the in vitro cocktail dosing method could be developed for evaluating the human BBB function. In addition, in vivo microdialysis method with cocktail-dosing could be developed. The latter method will be important for making the preclinical study more efficient. 2) We could gain the important information about a novel and flow-based cultivation method with shear stress.

Report

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

    (32 results)

All 2016 2015 2014 2013 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 5 results) Presentation (18 results) (of which Int'l Joint Research: 4 results) Book (4 results) Remarks (3 results)

  • [Journal Article] Cocktail-Dosing Microdialysis Study to Simultaneously Assess Delivery of Multiple Organic-Cationic Drugs to the Brain2016

    • Author(s)
      Atsushi Kitamura, Takashi Okura, Kei Higuchi, Yoshiharu Deguchi
    • Journal Title

      J. Pharm. Sci.

      Volume: 105 Issue: 2 Pages: 935

    • DOI

      10.1002/jps.24691

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The Blood-Brain Barrier Transport Mechanism Controlling Analgesic Effects of Opioid Drugs in CNS2015

    • Author(s)
      黄倉 崇、樋口 慧、出口芳春
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 135 Issue: 5 Pages: 697-702

    • DOI

      10.1248/yakushi.14-00234-2

    • NAID

      130005066918

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2015-05-01
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Memantine transport by a proton-coupled organic cation antiporter in hCMEC/D3 cells, an in vitro human blood-brain barrier model2015

    • Author(s)
      Higuchi K, Kitamura A, Okura T, Deguchi Y
    • Journal Title

      Drug Metab Pharmacokinet

      Volume: 30 Issue: 2 Pages: 182

    • DOI

      10.1016/j.dmpk.2014.12.006

    • NAID

      210000180315

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transport characteristics of tramadol in the blood-brain barrier2014

    • Author(s)
      Atsushi Kitamura, Kei Higuchi, Takashi Okura, Yoshiharu Deguchi
    • Journal Title

      J. Pharm. Sci.

      Volume: 103 Issue: 10 Pages: 3335

    • DOI

      10.1002/jps.24129

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Proton-Coupled Organic Cation Antiporter-Mediated Uptake of Apomorphine Enantiomers in Human Brain Capillary Endothelial Cell Line hCMEC/D32014

    • Author(s)
      Okura T, Higuchi K, Kitamura A, Deguchi Y
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 37 Issue: 2 Pages: 286-291

    • DOI

      10.1248/bpb.b13-00773

    • NAID

      130003382121

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endothelin-1 Receptors in Rat Tissues: Characterization by Bosentan, Ambrisentan and CI-10202014

    • Author(s)
      Yokoyama Y, Osano A, Hayashi H, Itoh K, Okura T, Deguchi Y, Ito Y, Yamada S
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 37 Issue: 3 Pages: 461-465

    • DOI

      10.1248/bpb.b13-00881

    • NAID

      130003390952

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Functional Expression of Organic Cation/carnitine Transporter 2 (OCTN2/<i>SLC22A5)</i> in Human Brain Capillary Endothelial Cell Line hCMEC/D3, a Human Blood-brain Barrier Model2014

    • Author(s)
      Okura T, Kato S, Deguchi Y
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 29 Issue: 1 Pages: 69-74

    • DOI

      10.2133/dmpk.DMPK-13-RG-058

    • NAID

      130004463347

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Memantine uptake mediated by a functionally diverse proton-coupled organic cation antiporter in human brain endothelial cells2015

    • Author(s)
      Higuchi K, Okura T, Deguchi Y
    • Organizer
      The Asian Federation for Pharmaceutical Sciences (AFPS) Conference 2015
    • Place of Presentation
      Bangkok (Thailand)
    • Year and Date
      2015-11-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Histamine H1-receptor signaling in human blood-brain barrier cells2015

    • Author(s)
      Okura T, Higuchi K, Ueno M, Ito H, Kondo A, Deguchi Y
    • Organizer
      第30回日本薬物動態学会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] Gene expression profiles in hCMEC/D3 cells with different transport activities of proton/organic cation antiporter2015

    • Author(s)
      Higuchi K, Okura T, Uematsu Y, Kondo A, Ito H, Deguchi Y
    • Organizer
      第30回日本薬物動態学会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] Analysis of gene expression profiles related to the transport activity of the proton/organic cation antiport system in hCMEC/D3 cells2015

    • Author(s)
      Higuchi K, Okura T, Uematsu Y, Kondo A, Ito H, Deguchi Y
    • Organizer
      Barcelona BioMed Conference, Blood Brain Barrier
    • Place of Presentation
      Barcelona (Spain)
    • Year and Date
      2015-11-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Involvement of functionally diverse proton-coupled organic cation antiporter in blood-brain barrier transport of memantine2015

    • Author(s)
      Higuchi K, Kitamura A, Okura T, Deguchi Y
    • Organizer
      11th International Conference on Cerebral Vascular Biology
    • Place of Presentation
      Paris (France)
    • Year and Date
      2015-07-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Blood-to-brain transport of apomorphine enantiomers by proton-coupled organic cation antiporter at the blood-brain barrier2015

    • Author(s)
      Okura T, Higuchi K, Kitamura A, Deguchi Y
    • Organizer
      11th International Conference on Cerebral Vascular Biology
    • Place of Presentation
      Paris (France)
    • Year and Date
      2015-07-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IN VIVO AND IN VITRO TRANSPORT OF APOMORPHINE ENANTIOMERS ACROSS THE BLOOD-BRAIN BARRIER2014

    • Author(s)
      Kitamura A, Higuchi K, Okura T, Deguchi Y
    • Organizer
      19th North American ISSX Meeting and 29th JSSX Annual Meeting
    • Place of Presentation
      San Francisco
    • Year and Date
      2014-10-19 – 2014-10-23
    • Related Report
      2014 Research-status Report
  • [Presentation] TRANSPORT CHARACTERISTICS OF TRAMADOL AT THE BLOOD-BRAIN BARRIER2014

    • Author(s)
      Deguchi Y, Kitamura A, Higuchi K, Okura T
    • Organizer
      19th North American ISSX Meeting and 29th JSSX Annual Meeting
    • Place of Presentation
      San Francisco
    • Year and Date
      2014-10-19 – 2014-10-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 脳マイクロダイアリシス法による薬物カクテルの脳移行性評価2014

    • Author(s)
      北村敦、黒澤俊樹、樋口慧、黄倉崇、福島貴人、祖父江佳奈、出口芳春
    • Organizer
      第58回薬学会関東支部大会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-04
    • Related Report
      2014 Research-status Report
  • [Presentation] アポモルヒネの高い脳移行性を担う血液脳関門輸送のインビボ解析2014

    • Author(s)
      黄倉 崇、佐藤樹夏、樋口 慧、北村 敦、柄谷礼人、久保敬史、小林俊生、櫻庭美菜子、出口芳春
    • Organizer
      第58回薬学会関東支部大会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-04
    • Related Report
      2014 Research-status Report
  • [Presentation] 脳マイクロダイアリシス法を用いたカクテル投与による薬物の脳移行性評価2014

    • Author(s)
      北村敦、樋口慧、黄倉崇、祖父江佳奈、福島貴人、出口芳春
    • Organizer
      日本薬剤学会第29年回
    • Place of Presentation
      埼玉
    • Year and Date
      2014-05-20 – 2014-05-22
    • Related Report
      2014 Research-status Report
  • [Presentation] hCMEC/D3細胞を用いたカクテル法によるH+/有機カチオン交換輸送体基質探索の基礎的検討2014

    • Author(s)
      樋口 慧、北村 敦、黄倉 崇、出口芳春
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学(熊本)
    • Related Report
      2013 Research-status Report
  • [Presentation] トランスポーターを利用した薬物の脳移行 -ヒト血液脳関門におけるメマンチンの輸送機構解析-2013

    • Author(s)
      樋口 慧、黄倉 崇、出口芳春
    • Organizer
      日本薬剤学会第28年会
    • Place of Presentation
      ウインク愛知(名古屋)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト血液脳関門におけるアポモルヒネのプロトン交換輸送機構2013

    • Author(s)
      黄倉 崇、樋口 慧、出口芳春
    • Organizer
      日本薬剤学会第28年会
    • Place of Presentation
      ウインク愛知(名古屋)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト血液脳関門細胞hCMEC/D3におけるメマンチンの輸送特性2013

    • Author(s)
      樋口 慧、北村 敦、黄倉 崇、出口芳春
    • Organizer
      日本薬物動態学会第28年会
    • Place of Presentation
      タワーホール船堀(東京)
    • Related Report
      2013 Research-status Report
  • [Presentation] プロトン交換輸送体によるアポモルヒネのヒト血液脳関門輸送

    • Author(s)
      黄倉 崇、樋口 慧、北村 敦、出口芳春
    • Organizer
      日本薬物動態学会第28年会
    • Place of Presentation
      タワーホール船堀(東京
    • Related Report
      2013 Research-status Report
  • [Presentation] A proton-coupled organic cation antiporter mediated transport of apomorphine in human brain capillary endothelial cell line hCMEC/D3

    • Author(s)
      Takashi Okura, Kei Higuchi, Atsushi Kitamura, Yoshiharu Deguchi
    • Organizer
      第7回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      東北大学片平キャンパス(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト血液脳関門のトラマドール輸送における

    • Author(s)
      北村 敦、樋口 慧、黄倉 崇、出口 芳春
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      帝京大学板橋キャンパス(東京)
    • Related Report
      2013 Research-status Report
  • [Book] コンパス生物薬剤学2016

    • Author(s)
      出口芳春
    • Total Pages
      7
    • Publisher
      南江堂
    • Related Report
      2015 Annual Research Report
  • [Book] 薬の生体内運命(改訂第6版)2015

    • Author(s)
      出口芳春
    • Total Pages
      22
    • Publisher
      ネオメディカル
    • Related Report
      2014 Research-status Report
  • [Book] 薬物分布実験法 脳関門2014

    • Author(s)
      黄倉崇、出口芳春
    • Total Pages
      13
    • Publisher
      南江堂
    • Related Report
      2013 Research-status Report
  • [Book] 細胞工学 トロイの木馬抗体を用いた中枢作用型タンパク質・遺伝子医薬開発の最前線2013

    • Author(s)
      黄倉崇、出口芳春
    • Total Pages
      2
    • Publisher
      秀潤社
    • Related Report
      2013 Research-status Report
  • [Remarks] 帝京大学薬学部

    • URL

      http://www.pharm.teikyo-u.ac.jp

    • Related Report
      2015 Annual Research Report
  • [Remarks] 帝京大学薬学部

    • URL

      http://www.pharm.teikyo-u.ac.jp/

    • Related Report
      2014 Research-status Report
  • [Remarks] 帝京大学薬学部ホームページ

    • URL

      http://www.pharm.teikyo-u.ac.jp/

    • Related Report
      2013 Research-status Report

URL: 

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

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