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Participation of OATP4C1 in the pharmacokinetics of drugs

Research Project

Project/Area Number 18K06742
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 InstitutionYamagata University (2019-2020)
Tohoku University (2018)

Principal Investigator

Yamaguchi Hiroaki  山形大学, 医学部, 教授 (80400373)

Co-Investigator(Kenkyū-buntansha) 阿部 高明  東北大学, 医工学研究科, 教授 (80292209)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords腎排泄 / トランスポーター / 相互作用 / 薬物動態 / OATP4C1 / 薬物相互作用
Outline of Final Research Achievements

To clarify the pharmacokinetic importance of the organic anion transporter OATP4C1 in the renal excretion process of drugs, transport analysis using OATP4C1 stably expressing cells was conducted. The results showed that some HIV protease inhibitors, new quinolones, and remdesivir inhibited OATP4C1-mediated transport. Furthermore, ritonavir, levofloxacin, and remdesivir were found to be substrates of OATP4C1 transport, suggesting the involvement of OATP4C1 in the pharmacokinetics of these drugs, especially in the renal excretion process.

Academic Significance and Societal Importance of the Research Achievements

臨床における医薬品適正使用のためのエビデンスを構築するため、未だ情報が十分蓄積されているとはいえない腎臓特異的有機アニオントランスポーターOATP4C1について、その薬物動態学的重要性を明らかにすることを目的として研究を実施した。本研究では、OATP4C1の新たな輸送基質の発見ならびにOATP4C1を介した薬物間相互作用を引きおこす可能性がある薬物を同定することに成功した。

Report

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

    (39 results)

All 2021 2020 2019 2018 Other

All Journal Article (23 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 22 results,  Open Access: 9 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] Azelnidipine treatment reduces the expression of Cav1.2 protein2021

    • Author(s)
      Fumiaki Nasu, Yutaro Obara, Yosuke Okamoto, Hiroaki Yamaguchi, Kazuya Kurakami, Ikuo Norota, Kuniaki Ishi
    • Journal Title

      Life Sciences

      Volume: 269 Pages: 119043-119043

    • DOI

      10.1016/j.lfs.2021.119043

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Simultaneous analysis of drugs administered to lung-transplanted patients using liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring2021

    • Author(s)
      Shinya Takasaki, Tensei Hirasawa, Yu Sato, Masamitsu Maekawa, Taku Tsukamoto, Masafumi Kikuchi, Jiro Ogura, Yoshihiro Hayakawa, Yasushi Matsuda, Hisashi Oishi, Tetsu Sado, Masafumi Noda, Yoshinori Okada, Hiroaki Yamaguchi, Nariyasu Mano
    • Journal Title

      Biomedical Chromatography

      Volume: 35 Issue: 6 Pages: 1-8

    • DOI

      10.1002/bmc.5067

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasma mycophenolic acid concentration and the clinical outcome after lung transplantation2020

    • Author(s)
      Yabuki Hiroshi、Matsuda Yasushi、Watanabe Tatsuaki、Eba Shunsuke、Hoshi Fumihiko、Hirama Takashi、Oishi Hisashi、Sado Tetsu、Noda Masafumi、Sakurada Akira、Kikuchi Masafumi、Yamaguchi Hiroaki、Mano Nariyasu、Okada Yoshinori
    • Journal Title

      Clinical Transplantation

      Volume: 34 Issue: 12 Pages: 1-9

    • DOI

      10.1111/ctr.14088

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ATP-binding cassette transporter C4 is a prostaglandin D2 exporter in HMC-1 cells2020

    • Author(s)
      Nobuaki Tanaka, Junya Kawai, Noriyasu Hirasawa, Nariyasu Mano, Hiroaki Yamaguchi
    • Journal Title

      Prostaglandins, Leukotrienes & Essential Fatty Acids

      Volume: 159 Pages: 102139-102139

    • DOI

      10.1016/j.plefa.2020.102139

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a precise quantitative method for monitoring sirolimus in whole blood using LC/ESI?MS/MS2020

    • Author(s)
      Shigeta Kensuke、Kikuchi Masafumi、Tanaka Masaki、Takasaki Shinya、Oishi Hisashi、Sado Tetsu、Matsuda Yasushi、Noda Masafumi、Okada Yoshinori、Mano Nariyasu、Yamaguchi Hiroaki
    • Journal Title

      Biomedical Chromatography

      Volume: 34 Issue: 8 Pages: 1-8

    • DOI

      10.1002/bmc.4853

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Risk Factors for Severe Hyponatremia Related to Cisplatin: A Retrospective Case-Control Study2019

    • Author(s)
      Shiro Hatakeyama, Toshihiro Shida, Hiroaki Yamaguchi
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 11 Pages: 1891-1897

    • DOI

      10.1248/bpb.b19-00477

    • NAID

      130007740636

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-11-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Limited Sampling Strategy for the Estimation of Mycophenolic Acid and its Acyl Glucuronide Metabolite Area under the Concentration-Time Curve in Japanese Lung Transplant Recipients2019

    • Author(s)
      Masaki Tanaka, Masafumi Kikuchi, Shinya Takasaki, Tensei Hirasawa, Kensuke Shigeta, Aoi Noda, Miki Akiba, Yasushi Matsuda, Hisashi Oishi, Tetsu Sado, Masafumi Noda, Yoshinori Okada, Nariyasu Mano, Hiroaki Yamaguchi
    • Journal Title

      Journal of Pharmacy and Pharmaceutical Sciences

      Volume: 22 Pages: 407-417

    • DOI

      10.18433/jpps30505

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of a Highly Potent Analogue and a Long-Acting Analogue of Oxytocin for the Treatment of Social Impairment-Like Behaviors2019

    • Author(s)
      Ichinose W, Cherepanov SM, Shabalova AA, Yokoyama S, Yuhi T, Yamaguchi H, Watanabe A, Yamamoto Y, Okamoto H, Horike S, Terakawa J, Daikoku T, Watanabe M, Mano N, Higashida H, Shuto S
    • Journal Title

      J Med Chem

      Volume: - Issue: 7 Pages: 3297-3310

    • DOI

      10.1021/acs.jmedchem.8b01691

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease2019

    • Author(s)
      Kikuchi Koichi、Saigusa Daisuke、Kanemitsu Yoshitomi、Matsumoto Yotaro、Tsukamoto Hiroki、Abe Takaaki
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1835-1835

    • DOI

      10.1038/s41467-019-09735-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of conjugated and unconjugated bile acid transport via human organic solute transporter α/β2019

    • Author(s)
      Suga Takahiro、Yamaguchi Hiroaki、Ogura Jiro、Mano Nariyasu
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: 1861 Issue: 5 Pages: 1023-1029

    • DOI

      10.1016/j.bbamem.2019.03.003

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnostic performance evaluation of sulfate-conjugated cholesterol metabolites as urinary biomarkers of Niemann-Pick disease type C2019

    • Author(s)
      Masamitsu Maekawa, Aya Narita, Isamu Jinnoh, Takashi Iida, Thorsten Marquardt, Eugen Mengel, Yoshikatsu Eto, Peter T. Clayton, Hiroaki Yamaguchi, Nariyasu Mano
    • Journal Title

      Clinica Chimica Acta

      Volume: 494 Pages: 58-63

    • DOI

      10.1016/j.cca.2019.03.1610

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Altered bile acid composition and disposition in a mouse model of non-alcoholic steatohepatitis2019

    • Author(s)
      Takahiro Suga, Hiroaki Yamaguchi, Jiro Ogura, Saori Shoji, Masamitsu Maekawa, Nariyasu Mano
    • Journal Title

      Toxicology and Applied Pharmacology

      Volume: 379 Pages: 114664-114664

    • DOI

      10.1016/j.taap.2019.114664

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Organogermanium suppresses cell death due to oxidative stress in normal human dermal fibroblasts2019

    • Author(s)
      Tomoya Takeda, Sota Doiyama, Junya Azumi, Yasuhiro Shimada, Yoshihiko Tokuji, Hiroaki Yamaguchi, Kosuke Nagata, Naoya Sakamoto, Hisashi Aso, Takashi Nakamura
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 13637-13637

    • DOI

      10.1038/s41598-019-49883-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Estimation of Blood Sirolimus Concentration Based on Tacrolimus Concentration/Dose Normalized by Body Weight Ratio in Lung Transplant Patients2019

    • Author(s)
      Masafumi Kikuchi, Kensuke Shigeta, Masaki Tanaka, Shinya Takasaki, Miki Akiba, Hisashi Oishi, Tetsu Sado, Yasushi Matsuda, Masafumi Noda, Yoshinori Okada, Nariyasu Mano, Hiroaki Yamaguchi
    • Journal Title

      Therapeutic Drug Monitoring

      Volume: 41 Issue: 5 Pages: 615-619

    • DOI

      10.1097/ftd.0000000000000649

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of H+-gradient dependent transporter in PGE2 release from A549 cells2019

    • Author(s)
      Nobuaki Tanaka, Hiroaki Yamaguchi, Nariyasu Mano
    • Journal Title

      Prostaglandins Leukot Essent Fatty Acids

      Volume: 149 Pages: 30-36

    • DOI

      10.1016/j.plefa.2019.08.003

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural determination of lysosphingomyelin-509 and discovery of novel class lipids from patients with niemann–pick disease type C2019

    • Author(s)
      Masamitsu Maekawa, Isamu Jinnoh, Yotaro Matsumoto, Aya Narita, Ryuichi Mashima, Hidenori Takahashi, Anna Iwahori, Daisuke Saigusa, Kumiko Fujii, Ai Abe, Katsumi Higaki, Shosei Yamauchi, Yuji Ozeki, Peter T Clayton, Hiroaki Yamaguchi, Nariyasu Mano, et al.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 20 Pages: 5018-5018

    • DOI

      10.3390/ijms20205018

    • URL

      https://localhost/en/publications/0001eeaa-b3d0-44fb-bd40-42657503d092

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Investigation of diagnostic performance of five urinary cholesterol metabolites for Niemann-Pick disease type C2019

    • Author(s)
      Masamitsu Maekawa, Isamu Jinnoh, Aya Narita, Takashi Iida, Daisuke Saigusa, Anna Iwahori, Hiroshi Nittono, Torayuki Okuyama, Yoshikatsu Eto, Kousaku Ohno, Peter T. Clayton, Hiroaki Yamaguchi, Nariyasu Mano
    • Journal Title

      Journal of Lipid Research

      Volume: 60 Issue: 12 Pages: 2074

    • DOI

      10.1194/jlr.m093971

    • URL

      https://pure.teikyo.jp/en/publications/2a56ddfc-9203-4fcf-97fe-f1fb7c24b668

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS2019

    • Author(s)
      Kanemitsu Yoshitomi、Mishima Eikan、Maekawa Masamitsu、Matsumoto Yotaro、Saigusa Daisuke、Yamaguchi Hiroaki、Ogura Jiro、Tsukamoto Hiroki、Tomioka Yoshihisa、Abe Takaaki、Mano Nariyasu
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 19075-19075

    • DOI

      10.1038/s41598-019-55600-1

    • URL

      https://pure.teikyo.jp/en/publications/ef660f70-40b0-4daf-a053-b1a892171a5c

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term relationship between everolimus blood concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma: a prospective study2019

    • Author(s)
      Takasaki Shinya、Yamaguchi Hiroaki、Kawasaki Yoshihide、Kikuchi Masafumi、Tanaka Masaki、Ito Akihiro、Mano Nariyasu
    • Journal Title

      Journal of Pharmaceutical Health Care and Sciences

      Volume: 5 Issue: 1 Pages: 6-6

    • DOI

      10.1186/s40780-019-0135-5

    • Related Report
      2018 Research-status Report
  • [Journal Article] Functional characterization of 40 CYP2B6 allelic variants by assessing efavirenz 8-hydroxylation2018

    • Author(s)
      Watanabe Takashi、Saito Takahiro、Rico Evelyn Marie Gutierrez、Hishinuma Eiji、Kumondai Masaki、Maekawa Masamitsu、Oda Akifumi、Saigusa Daisuke、Saito Sakae、Yasuda Jun、Nagasaki Masao、Minegishi Naoko、Yamamoto Masayuki、Yamaguchi Hiroaki、Mano Nariyasu、Hirasawa Noriyasu、Hiratsuka Masahiro
    • Journal Title

      Biochemical Pharmacology

      Volume: 156 Pages: 420-430

    • DOI

      10.1016/j.bcp.2018.09.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional Characterization of 21 Allelic Variants of Dihydropyrimidine Dehydrogenase Identified in 1070 Japanese Individuals2018

    • Author(s)
      Hishinuma Eiji、Narita Yoko、Saito Sakae、Maekawa Masamitsu、Akai Fumika、Nakanishi Yuya、Yasuda Jun、Nagasaki Masao、Yamamoto Masayuki、Yamaguchi Hiroaki、Mano Nariyasu、Hirasawa Noriyasu、Hiratsuka Masahiro
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 46 Issue: 8 Pages: 1083-1090

    • DOI

      10.1124/dmd.118.081737

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of PETINIA and LC-MS/MS for determining plasma mycophenolic acid concentrations in Japanese lung transplant recipients2018

    • Author(s)
      Kikuchi Masafumi、Tanaka Masaki、Takasaki Shinya、Takahashi Akiko、Akiba Miki、Matsuda Yasushi、Noda Masafumi、Hisamichi Kanehiko、Yamaguchi Hiroaki、Okada Yoshinori、Mano Nariyasu
    • Journal Title

      Journal of Pharmaceutical Health Care and Sciences

      Volume: 4 Issue: 1 Pages: 7-7

    • DOI

      10.1186/s40780-018-0101-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of clinical factors and UGT1A9 and CYP2B6 genotype on inter-individual differences in propofol pharmacokinetics2018

    • Author(s)
      Kanaya Akihiro、Sato Toshihiro、Fuse Nobuo、Yamaguchi Hiroaki、Mano Nariyasu、Yamauchi Masanori
    • Journal Title

      Journal of Anesthesia

      Volume: 32 Issue: 2 Pages: 236-243

    • DOI

      10.1007/s00540-018-2470-3

    • NAID

      40021526163

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 手術不能または再発乳がんに対するCDK4/6阻害薬パルボシクリブの臨床判断分析を用いた臨床評価2021

    • Author(s)
      金子基子、志田敏宏、荒川一郎、澤田広樹、小倉次郎、山口浩明、井上忠夫
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 新型コロナウイルス感染症治療薬レムデシビルおよびGS-441524の腎排泄および薬物相互作用におけるOATP4C1の役割2021

    • Author(s)
      佐藤紀宏、前川正充、阿部高明、山口浩明、眞野成康
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肺移植後患者における薬物療法個別化に向けて2020

    • Author(s)
      山口浩明
    • Organizer
      日本病院薬剤師会東北ブロック第10回学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] JADERを用いた白金系抗がん薬投与による低ナトリウム血症に関連した中枢神経症状の検討2020

    • Author(s)
      畠山史朗、加藤祐太、小原拓、志田敏宏、山口浩明
    • Organizer
      日本病院薬剤師会東北ブロック第10回学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヘム生合成系初発酵素5-アミノレブリン酸合成酵素1(ALAS1)遺伝子破壊マウスにおけるグルコース刺激インスリン分泌異常2020

    • Author(s)
      武田和也、van Wilk Koen、木村朋寛、岡野聡、斉藤真一、山口浩明、児玉健、高橋研、田中徹、中島元夫、中島修
    • Organizer
      第93回日本生化学学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 経口がん分子標的薬の個別化投与設計に向けた取り組み2019

    • Author(s)
      山口 浩明、髙﨑 新也、菊地 正史、川崎 芳英、伊藤 明宏、眞野 成康
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 急性薬毒物分析を保険診療の面から考える~現状と可能性~2019

    • Author(s)
      山口 浩明
    • Organizer
      第41回日本中毒学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト血漿中脂肪酸ヒドロキシ化脂肪酸の定量法の開発2019

    • Author(s)
      山口 浩明、渡邉 亜侑、眞野 成康
    • Organizer
      第30回日本臨床化学会東北支部総会
    • Related Report
      2019 Research-status Report
  • [Presentation] イヌサフラン誤食によりコルヒチン中毒を発症した患者への薬剤師の関わり2019

    • Author(s)
      矢内 一成、鈴木 博也、小林 正和、赤坂 和俊、山口 浩明、眞野 成康
    • Organizer
      第29回日本医療薬学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Pharmacokinetic analysis based on clinical chemistry2019

    • Author(s)
      Hiroaki Yamaguchi
    • Organizer
      The International Symposium of Health Care Technology, Drug Discovery and Chemical Biology 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] スニチニブのTDM普及に向けて2019

    • Author(s)
      山口浩明、髙﨑新也、菊地正史、川崎芳英、荒井陽一、眞野成康
    • Organizer
      日本臨床腫瘍薬学会学術大会2019
    • Related Report
      2018 Research-status Report
  • [Presentation] 臨床化学研究における質量分析の貢献 治療効果の最大化を目指した経口抗がん薬の治療薬物モニタリング2018

    • Author(s)
      高崎新也、川崎芳英、菊地正史、田中雅樹、山口浩明、眞野成康
    • Organizer
      第43回日本医用マススペクトル学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] トランスポーターを介した経口分子標的抗がん薬の相互作用2018

    • Author(s)
      山口浩明、眞野成康
    • Organizer
      第28回日本医療薬学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 東北病院薬剤師会員の学術研究に関する実態調査2018

    • Author(s)
      山口浩明、小林智徳、小原拓、赤嶺由美子、朝賀純一、芦埜和幸、 大原宏司、大村雅之、田村健悦、富岡佳久、豊口禎子、藤原洋之、 細井一広、渡辺剛
    • Organizer
      日本病院薬剤師会東北ブロック第8回学術大会
    • Related Report
      2018 Research-status Report
  • [Remarks] 山形大学医学部附属病院薬剤部ホームページ

    • URL

      https://www.yuhp-yaku.com/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 山形大学医学部附属病院薬剤部ホームページ

    • URL

      http://www.id.yamagata-u.ac.jp/Pharmacy/Pharm.html

    • Related Report
      2019 Research-status Report

URL: 

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

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