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Establishment of appropriate management of anti-HIV drugs to suppress the onset of HIV-associated neurocognitive disorder (HAND)

Research Project

Project/Area Number 18K06747
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionKyoto University

Principal Investigator

Tsuda Masahiro  京都大学, 薬学研究科, 講師 (10726813)

Co-Investigator(Kenkyū-buntansha) 山下 富義  京都大学, 薬学研究科, 教授 (30243041)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords抗HIV薬 / インテグラーゼ阻害薬 / トランスポーター / BCRP / P-gp / 血液脳関門 / HIV関連神経認知障害 / 有害事象自発報告データベース / 脂溶性 / 脳移行 / トランスポータ / HAND
Outline of Final Research Achievements

In the present study, we aimed to clarify the involvement of drug efflux transporters in the brain trafficking process of integrase inhibitors, a class of anti-HIV drugs. We showed that dolutegravir and bictegravir are transported by the drug efflux transporter BCRP, and that raltegravir tends to be transported by BCRP. Pharmacokinetic experiments in mice revealed that drug transport via P-gp and BCRP is involved in the transfer of dolutegravir and raltegravir to the brain. These findings may provide useful information for avoiding neuropsychiatric adverse events in HIV infection.

Academic Significance and Societal Importance of the Research Achievements

HIVによる神経毒性を原因とするHIV関連神経認知障害(HAND)は、HIV感染患者の生存率の改善に伴い問題となってきている重大な合併症である。HANDの治療や予防において抗HIV薬の脳内への移行性が重要と言われている。本研究で得られた成果は、HIV治療のキードラッグであるインテグラーゼ阻害薬の脳内移行性を評価したものであり、HANDの発症抑制に有効な薬物選択法の構築に貢献するものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] A model-based comparative meta-analysis of the efficacy of dolutegravir-based and efavirenz-based regimens in HIV-infected patients2019

    • Author(s)
      Ota Ryosaku、Ishii Hiromu、Tsuda Masahiro、Higuchi Yuriko、Yamashita Fumiyoshi
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 25 Issue: 9 Pages: 687-694

    • DOI

      10.1016/j.jiac.2019.03.015

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sialyl LewisX mimic-decorated liposomes for anti-angiogenic everolimus delivery to E-selectin expressing endothelial cells2019

    • Author(s)
      Chantarasrivong Chanikarn、Higuchi Yuriko、Tsuda Masahiro、Yamane Yuuki、Hashida Mitsuru、Konishi Miku、Komura Naoko、Ando Hiromune、Yamashita Fumiyoshi
    • Journal Title

      RSC Advances

      Volume: 9 Issue: 36 Pages: 20518-20527

    • DOI

      10.1039/c9ra01943j

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Concentration and Glycoform of Rituximab in Plasma of Patients with B Cell Non-Hodgkin’s Lymphoma2019

    • Author(s)
      Yonezawa Atushi、Otani Yuki、Kitano Toshiyuki、Mori Mayuko、Masui Sho、Isomoto Yui、Tsuda Masahiro、Imai Satoshi、Ikemi Yasuaki、Denda Masaya、Sato Yuki、Nakagawa Shunsaku、Omura Tomohiro、Nakagawa Takayuki、Yano Ikuko、Hayakari Makoto、Takaori-Kondo Akifumi、Matsubara Kazuo
    • Journal Title

      Pharmaceutical Research

      Volume: 36 Issue: 6 Pages: 82-82

    • DOI

      10.1007/s11095-019-2624-5

    • NAID

      120006624113

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analysis of Glycoforms and Amino Acids in Infliximab and a Biosimilar Product Using New Method with LC/TOF-MS2018

    • Author(s)
      Tsuda M, Otani Y, Yonezawa A, Masui S, Ikemi Y, Denda M, Sato Y, Nakagawa S, Omura T, Imai S, Nakagawa T, Hayakari M, Matsubara K.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 11 Pages: 1716-1721

    • DOI

      10.1248/bpb.b18-00491

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-11-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 抗HIV薬ドルテグラビルの吸収動態に対する薬物排出トランスポーターBCRPの寄与2020

    • Author(s)
      宇野瑞樹, 神谷武志, 津田真弘, 山下富義
    • Organizer
      日本薬剤学会 第35年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 薬物排出トランスポーターBCRP を介したインテグラーゼ阻害薬の輸送評価2019

    • Author(s)
      宇野瑞樹、神谷武志、津田真弘、山下富義
    • Organizer
      第69回日本薬学会関西支部総会・大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒアルロン酸修飾高分子ナノカプセルによる水溶性薬物のがん細胞内送達2018

    • Author(s)
      麻生寛人、樋口ゆり子、津田真弘、山下富義
    • Organizer
      第68回日本薬学会近畿支部総会・大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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