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Effect of renal dysfunction on the pharmacokinetics and pharmacodynamics of fluorouracil and its derivatives

Research Project

Project/Area Number 17K08446
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Matsubara Kazuo  京都大学, 医学研究科, 教授 (20127533)

Co-Investigator(Kenkyū-buntansha) 大村 友博  京都大学, 医学研究科, 助教 (00439035)
中川 俊作  京都大学, 医学研究科, 助教 (50721916)
今井 哲司  京都大学, 医学研究科, 講師 (80468579)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsスペシャルポピュレーション / 薬物動態 / 腎機能低下 / フッ化ピリミジン系抗がん薬 / 質量分析
Outline of Final Research Achievements

This study aimed to assess the changes in pharmacokinetics and pharmacodynamics of fluorouracil and its derivatives. We developed an analytical method to quantify the concentrations of fluorouracil and its metabolites in plasma and urine. Then, we examined the effect of renal dysfunction on the fluorouracil using rat models of renal disease. The result showed that the clearance of fluorouracil and its derivatives significantly decreased in rats of chronic kidney disease.

Academic Significance and Societal Importance of the Research Achievements

透析患者の増加に伴い、透析時にがんや慢性疾患を発症し薬物治療が選択される機会が増加している。一般に、腎機能低下時には薬物の体内動態が大きく変動し、有害反応のリスクが上昇するとされるが、詳細な検討は行われないまま不明であることが多い。そのため、重篤な有害反応を生じうる薬物に関して、腎機能 低下時における体内動態や有害反応のリスクを評価する研究を実施し、科学的根拠に基づいた薬物治療へとつなげることが重要な課題と考えられる。本研究では、腎機能低下時においてフッ化ピリミジン系抗がん剤の体内動態が変動すること示した。この結果、腎機能低下時における抗がん薬治療にあたって有用な情報を提供するものと考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (16 results)

All 2020 2019 2018 2017

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 5 results)

  • [Journal Article] Cisplatin, rather than oxaliplatin, increases paracellular permeability of LLC-PK1 cells via activating protein kinase C.2020

    • Author(s)
      Zhang Y, Yonezawa A, Nakagawa S, Imai S, Denda M, Omura T, Nakagawa T, Matsubara K.
    • Journal Title

      Drug Metab Pharmacokinet

      Volume: 35 Issue: 1 Pages: 111-116

    • DOI

      10.1016/j.dmpk.2019.09.001

    • NAID

      120006796498

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Schwann cell-derived CXCL1 contributes to human immunodeficiency virus type 1 gp120-induced neuropathic pain by modulating macrophage infiltration in mice2020

    • Author(s)
      Ntogwa Mpumelelo、Imai Satoshi、Hiraiwa Ren、Koyanagi Madoka、Matsumoto Mayuna、Ogihara Takashi、Nakagawa Shunsaku、Omura Tomohiro、Yonezawa Atsushi、Nakagawa Takayuki、Matsubara Kazuo
    • Journal Title

      Brain, Behavior, and Immunity

      Volume: in press Pages: 31233-4

    • DOI

      10.1016/j.bbi.2020.03.027

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of Pharmaceutical Formulation on the Mucosal Concentration of 5-Aminosalicylic Acid and <i>N</i>-Acetylmesalamine in Japanese Patients with Ulcerative Colitis2019

    • Author(s)
      Yamamoto Y, Masuda S, Nakase H, Matsuura M, Maruyama S, Hisamatsu T, Suzuki Y, Matsubara K.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 1 Pages: 81-86

    • DOI

      10.1248/bpb.b18-00561

    • NAID

      130007542208

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-01-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of fasting on warfarin sensitivity index in patients undergoing cardiovascular surgery.2019

    • Author(s)
      Katada Y, Nakagawa S, Nishimura A, Sato Y, Taue H, Matsumura K, Yamazaki K, Minakata K, Yano I, Omura T, Imai S, Yonezawa A, Sato Y, Nakagawa T, Minatoya K, Matsubara K.
    • Journal Title

      Eur J Clin Pharmacol

      Volume: 75 Issue: 4 Pages: 561-568

    • DOI

      10.1007/s00228-018-2592-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Minimal PBPK Model for Tacrolimus in Living-Donor Liver Transplantation : Perspectives related to Liver Regeneration and CYP3A5 genotype.2019

    • Author(s)
      Itohara K, Yano I, Tsuzuki T, Uesugi M, Nakagawa S, Yonezawa A, Okajima H, Kaido T, Uemoto S, Matsubara K.
    • Journal Title

      CPT : Pharmacometrics & Systems Pharmacology

      Volume: 8 Issue: 8 Pages: 587-595

    • DOI

      10.1002/psp4.12420

    • Description
      In press
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improvement of peripheral vascular impairment by a phosphodiesterase type 5 inhibitor tadalafil prevents oxaliplatin-induced peripheral neuropathy in mice2019

    • Author(s)
      Ogihara Takashi、Nakagawa Takayuki、Hayashi Maho、Koyanagi Madoka、Yonezawa Atsushi、Omura Tomohiro、Nakagawa Shunsaku、Kitada Noriaki、Imai Satoshi、Matsubara Kazuo
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 141 Issue: 4 Pages: 131-138

    • DOI

      10.1016/j.jphs.2019.10.005

    • NAID

      120006844940

    • Related Report
      2019 Annual Research 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
  • [Journal Article] Oxicam-derived non-steroidal anti-inflammatory drugs suppress 1-methyl-4-phenyl pyridinium-induced cell death via repression of endoplasmic reticulum stress response and mitochondrial dysfunction in SH-SY5Y cells.2018

    • Author(s)
      Omura T, Sasaoka M, Hashimoto G, Imai S, Yamamoto J, Sato Y, Nakagawa S, Yonezawa A, Nakagawa T, Yano I, Tasaki Y, Matsubara K.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 503 Issue: 4 Pages: 2963-2969

    • DOI

      10.1016/j.bbrc.2018.08.078

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics and Pharmacodynamics of Once-Daily Tacrolimus Compared With Twice-Daily Tacrolimus in the Early Stage After Living Donor Liver Transplantation.2018

    • Author(s)
      Iwasaki M, Yano I, Fukatsu S, Hashi S, Yamamoto Y, Sugimoto M, Fukudo M, Masuda S, Nakagawa S, Yonezawa A, Kaido T, Uemoto S, Matsubara K.
    • Journal Title

      Ther Drug Monit

      Volume: 40 Issue: 6 Pages: 675-681

    • DOI

      10.1097/ftd.0000000000000551

    • NAID

      120006559313

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of fasting on warfarin sensitivity index in patients undergoing cardiovascular surgery.2018

    • Author(s)
      Katada Y, Nakagawa S, Nishimura A, Sato YK, Taue H, Matsumura K, Yamazaki K, Minakata K, Yano I, Omura T, Imai S, Yonezawa A, Sato Y, Nakagawa T, Minatoya K, Matsubara K.
    • Journal Title

      Eur J Clin Pharmacol

      Volume: 75 Pages: 561-568

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of medication adherence on disease activity among Japanese patients with rheumatoid arthritis2018

    • Author(s)
      Nakagawa S, Nakaishi M, Hashimoto M, Ito H, Yamamoto W, Nakashima R, Tanaka M, Fujii T, Omura T, Imai S, Nakagawa T, Yonezawa A, Imai H, Mimori T, Matsubara K.
    • Journal Title

      PLoS One

      Volume: 13 Issue: 11 Pages: e0206943-e0206943

    • DOI

      10.1371/journal.pone.0206943

    • NAID

      120006539574

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemotherapy in cancer patients undergoing haemodialysis: a nationwide study in Japan.2018

    • Author(s)
      Funakoshi T, Horimatsu T, Nakamura M, Shiroshita K, Suyama K, Mukoyama M, Mizukami T, Sakurada T, Baba E, Tsuruya K, Nozaki A, Yahata K, Ozaki Y, Ubara Y, Yasui H, Yoshimoto A, Fukuma S, Kondo N, Matsubara T, Matsubara K, Fukuhara S, Yanagita M, Muto M.
    • Journal Title

      ESMO Open

      Volume: 23 Issue: 2 Pages: e000301-e000301

    • DOI

      10.1136/esmoopen-2017-000301

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacokinetic and Pharmacodynamic Markers of Mycophenolic Acid Associated with Effective Prophylaxis for Acute Graft-Versus-Host Disease and Neutrophil Engraftment in Cord Blood Transplant Patients2018

    • Author(s)
      Yoshimura Kazuaki、Yano Ikuko、Yamamoto Takashi、Kondo Tadakazu、Kawanishi Misaki、Isomoto Yui、Yonezawa Atsushi、Takaori-Kondo Akifumi、Matsubara Kazuo
    • Journal Title

      Biol. Blood Marrow Transplant.

      Volume: - Issue: 7 Pages: 1441-1448

    • DOI

      10.1016/j.bbmt.2018.01.040

    • NAID

      120006501237

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Accumulation of alpha-fluoro-beta-alanine and fluoro mono acetate in a patient with 5-fluorouracil-associated hyperammonemia.2017

    • Author(s)
      Nishikawa Y, Funakoshi T, Horimatsu T, Miyamoto S, Matsubara T, Yanagita M, Nakagawa S, Yonezawa A, Matsubara K, Muto M.
    • Journal Title

      Cancer Chemother Pharmacol.

      Volume: 79 Issue: 3 Pages: 619-633

    • DOI

      10.1007/s00280-017-3249-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Population pharmacokinetics of topiramate in Japanese pediatric and adult patients with epilepsy using routinely monitored data.2017

    • Author(s)
      Takeuchi M, Yano I, Ito S, Sugimoto M, Yamamoto S, Yonezawa A, Ikeda A,Matsubara K
    • Journal Title

      Therapeutic Drug Monitoring

      Volume: 39 Issue: 2 Pages: 124-131

    • DOI

      10.1097/ftd.0000000000000383

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2017-04-28   Modified: 2021-02-19  

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