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Prediction of the human brain distribution for the central nervous system drugs using a novel human immortalized brain capillary endothelial cells

Research Project

Project/Area Number 22590144
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
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)
KATO Sayaka  帝京大学, 薬学部, 助教 (70505940)
HIGUCHI Kei  帝京大学, 薬学部, 助教 (10625304)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords血液脳関門 / ヒト細胞株 / トランスポーター / カチオン性薬物 / 脳移行性 / 遺伝子解析 / スケールアップ / ヒト由来不死化細胞株 / RNAiライブラリー / 遺伝子抑制 / 輸送特性 / 発現解析
Research Abstract

Prediction of the brain distribution of drugs, based on the transport function of the human blood-brain barrier (BBB), is important for not only development of new central nervous system (CNS)-acting drugs, but also pharmacotherapy for CNS diseases. The purpose of this study is to clarify the functional expression of cation transporters using human brain capillary endothelial cell line hCMEC/D3 (D3), an in vitro model. The study was also investigated whether or not the results of in vitro uptake study using D3 cells can be extrapolated to human BBB. In this study, it was found that cationic transporters (OCTN2, OCTN1, PMAT and H^+/organic cation antiporter) are functionally expr essed in D3 cells. Further, a method can be established for extrapolating brain distribution of theCNS-acting drugs in human from the in vitro data using D3 cells.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (42 results)

All 2013 2012 2011 2010 Other

All Journal Article (14 results) (of which Peer Reviewed: 7 results) Presentation (22 results) Book (3 results) Remarks (3 results)

  • [Journal Article] Characterization of the carriermediated transport of ketoprofen, a nonsteroidal anti-inflammatory drug, in rabbit cornea epithelium cells2013

    • Author(s)
      Fujii S. Deguchi Y. et al
    • Journal Title

      J. Pharm. Pharmacol

      Volume: 65 Pages: 171-180

    • Related Report
      2012 Final Research Report
  • [Journal Article] Functional expression of a protoncoupled organic cation (H^+/OC) antiporter in humam brain capillary endothelial cell line hCMEC/D3, a human blood-brain barrier model2013

    • Author(s)
      Shimomura K, Okura T, Deguchi Y, et al
    • Journal Title

      Fluids. Barrier. CNS

      Volume: 10:8 Pages: 1-10

    • Related Report
      2012 Final Research Report
  • [Journal Article] Functional expression of a proton-coupled organic cation (H<sup>+</sup>/OC) antiporter in human brain capillary endothelial cell line hCMEC/D3, a human blood-brain barrier model2013

    • Author(s)
      Keita Shimomura, Takashi Okura, Sayaka Kato, Pierre-Olivier Couraud, Jean-Michel Scherrmann, Tetsuya Terasaki, Yoshiharu Deguchi
    • Journal Title

      Fluids and Barriers CNS

      Volume: 10 Issue: 1 Pages: 1-10

    • DOI

      10.1186/2045-8118-10-8

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of the carrier-mediated transport of ketorofen, a nonsteroidal anti-inflammatory drug, in rabbit corneal epithelim cells.2013

    • Author(s)
      Shinobu Fujii, Hideki Hayashi, Kunihiko Itoh, Shizuo Yamada, Yoshiharu Deguch, Kouichi Kawazu
    • Journal Title

      J. Pharm. Pharmacol.

      Volume: 65 Pages: 171-180

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Measurement of glomerular filtration rate by rapid intravenous injection of a newly developed insulin fraction2011

    • Author(s)
      Maeda Y and Deguchi Y et al
    • Journal Title

      J. Rural Med

      Volume: 6 Pages: 9-15

    • Related Report
      2012 Final Research Report
  • [Journal Article] The blood-brain barrier as a focus of drug metabolism and Pharmacokinetics2011

    • Author(s)
      Deguchi Y
    • Journal Title

      Drug Metab. Pharmacokin

      Volume: 26 Pages: 1-1

    • Related Report
      2012 Final Research Report
  • [Journal Article] Functional characterization of rat plasma membrane monoamine transporter in the blood-brain and blood-cerebrospinal fluid barriers2011

    • Author(s)
      Okura T and Deguchi Y et al
    • Journal Title

      J. Pharm. Sci

      Volume: 100 Pages: 3923-3938

    • Related Report
      2012 Final Research Report
  • [Journal Article] Diphenhydramine active uptake at the blood-brain barrier and its interaction with oxycodonein vitro and invivo2011

    • Author(s)
      Sadiq, MW and Deguchi Y et al
    • Journal Title

      J. Pharm. Sci

      Volume: 100 Pages: 3912-3923

    • Related Report
      2012 Final Research Report
  • [Journal Article] Diphenhydramine active uptake at the blood-brain barrier and its interaction with oxycodone in vitro and in vivo2011

    • Author(s)
      Sadiq, MW, Deguchi Y, et al
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 100 Issue: 9 Pages: 3912

    • DOI

      10.1002/jps.22567

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional characterization of rat plasma membrane monoamine transporter in the blood-brain and blood-cerebrospinal fluid barriers2011

    • Author(s)
      Okura, T., Yamashita, A., et al
    • Journal Title

      J.Pharm.Sci.

      Volume: 100 Issue: 9 Pages: 3924

    • DOI

      10.1002/jps.22594

    • URL

      https://pure.teikyo.jp/en/publications/d4547829-07c6-4ad1-8805-fa3be98e5456

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The blood-brain barrier as a focus of drug metabolism and pharmacokinetics2011

    • Author(s)
      Deguchi Y
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 26 Pages: 1-1

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Measurement of glomerular filtration rate by rapid intravenous injection of a newly developed insulin fraction2011

    • Author(s)
      Maeda Y, Deguchi Y, et al
    • Journal Title

      Journal of Rural Medicine

      Volume: 6 Pages: 9-15

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Drug-drug interaction between oxycodone and adjuvant analgesics in blood-brain barrier and antinociceptive effect2010

    • Author(s)
      Okura T, and Deguchi Y, et al
    • Journal Title

      J. Pharm. Sci

      Volume: 99 Pages: 467-474

    • Related Report
      2012 Final Research Report
  • [Journal Article] Drug-drug interaction between oxycodone and adjuvant analgesics in blood-brain barrier and antinociceptive effect.2010

    • Author(s)
      Okura T, Deguchi Y, et al.
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 99 Pages: 467-474

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 尿酸トランスポーターURAT1 の脳内局在解析2013

    • Author(s)
      富岡直子、出口芳春ら
    • Organizer
      日本薬学会第133 年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] 尿酸トランスポーターURAT1の脳内局在解析2013

    • Author(s)
      富岡 直子, 道志 勝, 市田 公美, 森崎 隆幸, 出口 芳春, 細山田 真
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒト脳毛細血管内皮細胞株 hCMEC/D3 を用いたカチオン性薬物のヒト血液脳関門透過性予測の試み2012

    • Author(s)
      黄倉 崇、樋口 慧、出口芳春ら
    • Organizer
      日本動物実験代替学会第25回大会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] Investigation of the organic cation/carnitine transporter in human brain endothelial cells by small interfering RNA2012

    • Author(s)
      Okura T and Deguchi Y
    • Organizer
      第27回日本薬物動態学会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] In vitro 試験に基いたヒト脳 D2 受容体占有率の予測2012

    • Author(s)
      呉 春勇、楠原洋之、出口芳春、杉山雄一
    • Organizer
      日本薬剤学会第27 年会
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒト脳毛細血管内皮細胞(hCMEC/D3) を用いた有機カチオン/カルニチントランスポーターの機能解析2012

    • Author(s)
      黄倉 崇、加藤清香、出口芳春
    • Organizer
      日本薬剤学会第27 年会
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report
  • [Presentation] The existence of H^+-coupled organic cation antiporter (the pyrilamine transporter) at the in vitro human blood-brain barrier cells2012

    • Author(s)
      Deguchi Y, et al
    • Organizer
      薬物動態国際シンポジューム
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] ヒト脳毛細血管内皮細胞(hCMEC/D3)を用いた有機カチオン/カルニチントランスポーターの機能解析2012

    • Author(s)
      黄倉 崇、加藤清香、出口芳春
    • Organizer
      日本薬剤学会第27年会
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
  • [Presentation] In vitro試験に基いたヒト脳D2受容体占有率の予測2012

    • Author(s)
      呉 春勇、楠原洋之、出口芳春、杉山雄一
    • Organizer
      日本薬剤学会第27年会
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒト脳毛細血管内皮細胞株hCMEC/D3を用いたカチオン性薬物のヒト血液脳関門透過性予測の試み2012

    • Author(s)
      黄倉崇、下村慶太、樋口 慧、Pierre-Oliver Couraud、出口芳春
    • Organizer
      日本動物実験代替学会第25回大会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒト血液脳関門細胞における有機カチオン関連トランスポーターの発現と機能2011

    • Author(s)
      黄倉崇、出口芳春ら
    • Organizer
      日本薬学会 131 年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] マウス血液脳関門およびグリア細胞におけるカチオントランスポーターの局在解析2011

    • Author(s)
      森本理代、出口芳春ら
    • Organizer
      日本薬学会 131年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] マウス血液脳関門およびグリア細胞におけるカチオントランスポーターの局在解析2011

    • Author(s)
      森本理代、出口芳春, ら
    • Organizer
      日本薬学会131年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヒト血液脳関門細胞における有機カチオン関連トランスポーターの発現と機能2011

    • Author(s)
      黄倉崇、出口芳春, ら
    • Organizer
      日本薬学会131年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Diphenhydramine active uptake at the blood-brain barrier and its interaction with oxycodone in vitro and in vivo2011

    • Author(s)
      Deguchi Y, et al
    • Organizer
      Asian Federation of Pharmaceutical Science 2011
    • Place of Presentation
      Kuala Lumpur
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] Localization and functional roles of organic cation/carnitine transporter at the blood-brain barrier2011

    • Author(s)
      Sayaka K, Deguchi Y, et al
    • Organizer
      第26回日本薬物動態学会年会
    • Place of Presentation
      広島
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] RNA 干渉法を用いたヒト血液脳関門細胞で機能する有機カチオン輸送体の探索2011

    • Author(s)
      黄倉 崇、 出口芳春ら
    • Organizer
      第6回トランスポーター研究会
    • Place of Presentation
      仙台
    • Related Report
      2012 Final Research Report
  • [Presentation] 脳関門システムにおけるカチオントランスポーターの局在解析2011

    • Author(s)
      森本理代、出口芳春ら
    • Organizer
      日本薬剤学会第26 年会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] RNA 干渉法を用いたヒト血液脳関門細胞における有機カチオン輸送体の機能解析2011

    • Author(s)
      黄倉 崇、出口芳春ら
    • Organizer
      日本薬剤学会第26 年会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] RNA干渉法を用いたヒト血液脳関門細胞における有機カチオン輸送体の機能解析2011

    • Author(s)
      黄倉崇、出口芳春, ら
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] 脳関門システムにおけるカチオントランスポーターの局在解析2011

    • Author(s)
      森本理代、出口芳春, ら
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] RNA干渉法を用いたヒト血液脳関門細胞で機能する有機カチオン輸送体の探索2011

    • Author(s)
      黄倉崇、出口芳春, ら
    • Organizer
      第6回トランスポーター研究会
    • Place of Presentation
      仙台
    • Related Report
      2011 Annual Research Report
  • [Book] 遺伝子医学 MOOK 別冊 -ペプチド・タンパク性医薬品の新規 DDS 製剤の開発と応用2011

    • Author(s)
      出口芳春
    • Total Pages
      280
    • Publisher
      メディカル・ドゥ
    • Related Report
      2012 Final Research Report
  • [Book] 遺伝子医学MOOK別冊-ペプチド・タンパク性医薬品の新規DDS製剤の開発と応用-2011

    • Author(s)
      出口芳春
    • Total Pages
      7
    • Publisher
      メディカル・ドゥ
    • Related Report
      2011 Annual Research Report
  • [Book] コンパス生物薬剤学(脳への移行、胎児への移行と胎盤関門)2010

    • Author(s)
      出口芳春
    • Publisher
      南江堂
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.pharm.teikyo-u.ac.jp/lab/dotai/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 帝京大学薬学部

    • URL

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

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.pharm.teikyo-u.ac.jp/lab/dotai/index.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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