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Development of the prediction system for tubular secretion of drugs in the human kidney

Research Project

Project/Area Number 18K06766
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 InstitutionRitsumeikan University

Principal Investigator

Katsura Toshiya  立命館大学, 薬学部, 教授 (10283615)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords薬物トランスポーター / 尿細管分泌 / 経細胞輸送 / 薬物相互作用 / 培養細胞 / 薬物動態学 / 腎排泄 / トランスポーター / in vitro評価
Outline of Final Research Achievements

At present, it is difficult to accurately predict the degree of tubular secretion involved in renal excretion of drugs and the contribution of drug transporters involved in tubular secretion. In this study, we examined the effect of expression of transcription factors involved in the regulation of drug transporter expression on the expression of drug transporters in human kidney-derived HK-2 cells. It was demonstrated that HK-2 cells stably expressing HNF1α showed a increased expression of megalin, which is responsible for endocytosis of low molecular weight proteins and drugs. The nephrotoxicity of aminoglycoside antibiotics, substrates of megalin, is significantly enhanced in HK-2 cells stably expressing HNF1α.

Academic Significance and Societal Importance of the Research Achievements

本研究は、薬物の腎移行動態を評価しうる評価系の構築を目指したものであり、ヒト腎由来HK-2細胞においてHNF1αを発現させることにより、メガリンの発現が上昇することを明らかにした。メガリンを恒常的に発現するヒト由来培養腎上皮細胞は存在しないことから、HNF1α安定発現HK-2細胞は、メガリンの機能評価やアミノグリコシド系抗生物質の腎毒性評価が可能なin vitro実験系となりうることが示唆され、今後の新薬開発においても有用な評価系となることが期待される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (31 results)

All 2022 2021 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (26 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Variation in Expression of Cytochrome P450 3A Isoforms and Toxicological Effects: Endo- and Exogenous Substances as Regulatory Factors and Substrates2021

    • Author(s)
      Fujino Chieri、Sanoh Seigo、Katsura Toshiya
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 44 Issue: 11 Pages: 1617-1634

    • DOI

      10.1248/bpb.b21-00332

    • NAID

      130008110315

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2021-11-01
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Administration of zinc to preterm infants with hypozincemia does not reduce serum copper concentrations in most cases: a single-center retrospective observational study2021

    • Author(s)
      Ito Toshikazu、Uenoyama Kazuya、Kobayashi Kazuhiro、Kakumoto Mikio、Mizumoto Hiroshi、Katsura Toshiya、Onoue Masahide
    • Journal Title

      Journal of Pharmaceutical Health Care and Sciences

      Volume: 7 Issue: 1

    • DOI

      10.1186/s40780-021-00229-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Population pharmacokinetics and pharmacodynamics of apixaban linking its plasma concentration to intrinsic activated coagulation factor X activity in Japanese patients with atrial fibrillation2019

    • Author(s)
      Ueshima Satoshi、Hira Daiki、Tomitsuka Chiho、Nomura Miki、Kimura Yuuma、Yamane Takuya、Tabuchi Yohei、Ozawa Tomoya、Itoh Hideki、Horie Minoru、Terada Tomohiro、Katsura Toshiya
    • Journal Title

      The AAPS Journal

      Volume: 21 Issue: 5 Pages: 80-80

    • DOI

      10.1208/s12248-019-0353-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic variants of alcohol‐metabolizing enzymes in Brugada syndrome: Insights into syncope after drinking alcohol2019

    • Author(s)
      Wu Qi、Hayashi Hideki、Hira Daiki、Sonoda Keiko、Ueshima Satoshi、Ohno Seiko、Makiyama Takeru、Terada Tomohiro、Katsura Toshiya、Miura Katsuyuki、Horie Minoru
    • Journal Title

      Journal of Arrhythmia

      Volume: 35 Issue: 5 Pages: 752-759

    • DOI

      10.1002/joa3.12227

    • NAID

      120006848263

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation.2018

    • Author(s)
      Ueshima S, Hira D, Kimura Y, Fujii R, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Ohno S, Horie M, Terada T, Katsura T.
    • Journal Title

      Br. J. Clin. Pharmacol.

      Volume: - Issue: 6 Pages: 1301-1312

    • DOI

      10.1111/bcp.13561

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト正常近位尿細管細胞HK-2におけるHepatocyte Nuclear Factor発現の影響2022

    • Author(s)
      田頭怜奈、結城詩央里、根来亮介、藤野智恵里、上島 智、藤田卓也、桂 敏也
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 薬物代謝酵素UGT1Aの発現低下が薬物トランスポーターの遺伝子発現に及ぼす影響2022

    • Author(s)
      藤野智恵里、荒井理佐子、上島 智、桂 敏也
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 急性および慢性関節炎モデルマウスにおけるシトクロムP450の発現変動2022

    • Author(s)
      林 紅瑠実、藤野智恵里、葛生泰己、上島 智、桂 敏也
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肝臓の炎症が薬物代謝酵素の発現誘導に及ぼす影響2022

    • Author(s)
      葛生泰己、藤野智恵里、林 紅瑠実、上島 智、桂 敏也
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 慢性関節炎モデルマウスにおけるシトクロムP450(CYP)の遺伝子発現変動2021

    • Author(s)
      林 紅瑠実、藤野智恵里、上島 智、桂 敏也
    • Organizer
      第71回日本薬学会関西支部大会・総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Impact of substrates and inhibitors of breast cancer resistance protein on apixaban pharmacokinetics in Japanese patients with atrial fibrillation2021

    • Author(s)
      Satoshi Ueshima, Daiki Hira, Karin Hirata, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Yoshihisa Nakagawa, Minoru Horie, Tomohiro Terada, Toshiya Katsura
    • Organizer
      第31回日本医療薬学会年会 (International Poster Session)、
    • Related Report
      2021 Annual Research Report
  • [Presentation] Population pharmacokinetics of edoxaban in Japanese patients with atrial fibrillation2021

    • Author(s)
      Sayana Matsuda, Satoshi Ueshima, Daiki Hira, Rio Michihata, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Moritake Iguchi, Masaharu Akao, Satoshi Shizuta, Takeshi Makiyama, Yoshihisa Nakagawa, Minoru Horie, Tomohiro Terada, Toshiya Katsura
    • Organizer
      第15回次世代を担う若手医療薬科学シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 関節炎モデルマウスにおける薬物代謝酵素および薬物トランスポーターの発現変動2021

    • Author(s)
      藤野智恵里、上島 智、桂 敏也
    • Organizer
      日本薬物動態学会第36回年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 直接作用型経口抗凝固薬の消化管出血リスクとPGx2021

    • Author(s)
      上島 智、桂 敏也
    • Organizer
      第42回日本臨床薬理学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 排泄トランスポーターMRP2の発現低下が薬物代謝酵素の遺伝子発現に与える影響2021

    • Author(s)
      藤野智恵里、上島 智、桂 敏也
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Edoxaban blood concentrations vary considerably and correlate with anti-factor Xa activity in atrial fibrillation patients2020

    • Author(s)
      Minoru Horie, Satoshi Ueshima, Daiki Hira, Toshiya Katsura, Tomohiro Terada, Kouichi Kato, Tomoya Ozawa, Hideki Itoh, Yohei Tabuchi, Miya Horie, Yoshihisa Nakagawa, Takeru Makiyama, Satoshi Shizuta, Asami Kashiwa, Takanori Aizawa, Takeshi Kimura, Moritake Iguchi, Masaharu Akao
    • Organizer
      第84回日本循環器学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 第Xa因子阻害薬の臨床薬物動態/ゲノム薬理学的研究2020

    • Author(s)
      上島 智、桂 敏也
    • Organizer
      第15回トランスポーター研究会年会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 心房細動患者におけるエドキサバンの母集団薬物動態/ゲノム薬理学的解析2020

    • Author(s)
      上島 智、平 大樹、道籏梨央、田淵陽平、伊藤英樹、小澤友哉、中川義久、堀江 稔、寺田智祐、桂 敏也
    • Organizer
      第30回日本医療薬学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Population pharmacokinetics and pharmacogenomics of rivaroxaban in Japanese patients with atrial fibrillation2020

    • Author(s)
      Satoshi Ueshima, Daiki Hira, Kenji Kuwata, Karin Hirata, Yohei Tabuchi, Hideki Itoh, Tomoya Ozawa, Yoshihisa Nakagawa, Minoru Horie, Tomohiro Terada, Toshiya Katsura
    • Organizer
      第30回日本医療薬学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] チカグレロルの代謝反応におけるCYP3A4/5の寄与に関する基礎的検討2019

    • Author(s)
      横井一駿、上島 智、藤野智恵里、桂 敏也
    • Organizer
      日本医療薬学会第3回フレッシャーズ・カンファランス
    • Related Report
      2019 Research-status Report
  • [Presentation] アピキサバン内服患者における乳癌耐性タンパク質 (ABCG2) を介した薬物間相互作用に関する検討2019

    • Author(s)
      平田華鈴、上島 智、平 大樹、田淵陽平、伊藤英樹、小澤友哉、中川義久、堀江 稔、寺田智祐、桂 敏也
    • Organizer
      医療薬学フォーラム2019/第27回クリニカルファーマシーシンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] アミオダロンの代謝におけるCYP3A4/5の寄与に関する基礎的検討2019

    • Author(s)
      岡 拓朗、上島 智、藤野智恵里、桂 敏也
    • Organizer
      第69回日本薬学会関西支部総会・大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 心房細動患者におけるリバーロキサバンの母集団薬物動態解析2019

    • Author(s)
      上島 智、平 大樹、桑田健司、平田華鈴、田淵陽平、伊藤英樹、小澤友哉、中川義久、堀江 稔、寺田智祐、桂 敏也
    • Organizer
      第29回日本医療薬学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Quantitative evaluation of the contribution of CYP3A4 and CYP3A5 to amiodarone pharmacokinetics in human from in vitro data2019

    • Author(s)
      岡 拓朗、上島 智、藤野智恵里、桂 敏也
    • Organizer
      日本薬物動態学会第34回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト組織におけるグルクロン酸抱合反応を考慮したエンタカポンの生理学的薬物速度論解析2018

    • Author(s)
      爲本雄太、上島 智、宮川幸典、目片茉柚、桂 敏也
    • Organizer
      日本薬剤学会 第33年会
    • Related Report
      2018 Research-status Report
  • [Presentation] リバーロキサバンの血中トラフ濃度に及ぼす薬物動態関連遺伝子多型の影響2018

    • Author(s)
      桑田健司、上島 智、平 大樹、山根拓也、芝口 彩、田淵陽平、伊藤英樹、小澤友哉、堀江 稔、寺田智祐、桂 敏也
    • Organizer
      医療薬学フォーラム2018/第26回クリニカルファーマシーシンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Population pharmacokinetics and pharmacodynamics of apixaban in Japanese patients with atrial fibrillation2018

    • Author(s)
      Satoshi Ueshima, Daiki Hira, Chiho Tomitsuka, Miki Nomura, Yuuma Kimura, Takuya Yamane, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Seiko Ohno, Minoru Horie, Tomohiro Terada, Toshiya Katsura
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生理学的薬物速度論に基づくエンタカポンの体内動態解析2018

    • Author(s)
      爲本雄太、上島 智、宮川幸典、目片茉柚、桂 敏也
    • Organizer
      日本医療薬学会第2回フレッシャーズ・カンファランス
    • Related Report
      2018 Research-status Report
  • [Presentation] アミオダロンの代謝に及ぼす血液凝固第Xa因子阻害薬の影響2018

    • Author(s)
      芝口 彩、上島 智、平田華鈴、平野尋大、桂 敏也
    • Organizer
      日本医療薬学会第2回フレッシャーズ・カンファランス
    • Related Report
      2018 Research-status Report
  • [Presentation] リバーロキサバンの血中濃度と臨床検査値及び薬物動態関連遺伝子多型の相関解析2018

    • Author(s)
      桑田健司、上島 智、平 大樹、山根拓也、田淵陽平、伊藤英樹、小澤友哉、堀江 稔、寺田智祐、桂 敏也
    • Organizer
      日本医療薬学会第2回フレッシャーズ・カンファランス
    • Related Report
      2018 Research-status Report
  • [Presentation] Association of genetic polymorphisms in drug transporters and enzymes with plasma concentrations of rivaroxaban in Japanese patients with atrial fibrillation2018

    • Author(s)
      Satoshi Ueshima, Daiki Hira, Takuya Yamane, Kenji Kuwata, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Minoru Horie, Tomohiro Terada, Toshiya Katsura
    • Organizer
      2018 International Meeting on 22nd Microsomes and Drug Oxidations and 33rd Japanese Society fot the Study of Xenobiotics
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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