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Relationship between blood concentration of ibrutinib and fungal infection

Research Project

Project/Area Number 20K16095
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionMeiji Pharmaceutical University

Principal Investigator

YASU TAKEO  明治薬科大学, 薬学部, 准教授 (30866950)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsイブルチニブ / 治療薬物モニタリング / 真菌感染症 / 医療ビックデータ
Outline of Research at the Start

イブルチニブは、造血器悪性腫瘍の患者に使用される内服の分子標的薬であり、死に至る可能性のある肺アスペルギルス症などの真菌感染症を誘発することが報告されている。しかしながら、イブルチニブを使用している患者における真菌感染症のリスク因子は明らかになっていない。本研究では、血中のイブルチニブの濃度などを用いて、真菌感染症のリスク因子を明らかにする。本研究の結果により、イブルチニブを使用する患者の真菌感染症の対策に繋げることで、真菌感染症にて命を落とす患者を減らすことが期待される。

Outline of Final Research Achievements

This study found that the incidence of fungal infections in patients with chronic lymphocytic leukemia (CLL) treated with the oral molecularly targeted drug ibrutinib was 9.2% in Japan, and that in patients with CLL treated with ibrutinib, prophylactic administration of antifungal drugs did not contribute to the prevention of ibrutinib-induced fungal infections. Furthermore, hemodialysis treatment did not significantly affect blood levels of ibrutinib in patients with CLL. The study also developed methods to measure blood levels of cabozantinib, sotrasib and olaparib, which are oral molecularly targeted drugs similar to ibrutinib.

Academic Significance and Societal Importance of the Research Achievements

日本では超高齢化に伴い造血器腫瘍の患者が増加し、造血器腫瘍の治療薬であるイブルチニブを使用する患者も増加することが予想されます。イブルチニブを使用することで真菌感染症を誘発することが知られており、本研究では、日本におけるイブルチニブの使用患者の真菌感染症の発症率や抗真菌薬による予防が有効ではないことを明らかにしたことで、イブルチニブを使用する患者の真菌に対する予防策を講じる際に役に立ちます。抗真菌薬による予防対策を実施しないことで、抗真菌薬の使用を減らし、薬剤耐性化の抑制に寄与できると考えています。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (12 results)

All 2023 2022 2021

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (3 results)

  • [Journal Article] Development of a simple high-performance liquid chromatography-ultraviolet detection method for olaparib in patients with ovarian cancer2023

    • Author(s)
      Yasu Takeo、Nishijima Ryosuke、Ikuta Risa、Shirota Mikio、Iwase Haruko
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 17 Issue: 6 Pages: 428-433

    • DOI

      10.5582/ddt.2023.01074

    • ISSN
      1881-7831, 1881-784X
    • Year and Date
      2023-12-31
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a simple high-performance liquid chromatography-ultraviolet method for sotorasib quantification in human plasma: Implications for therapeutic drug monitoring2023

    • Author(s)
      Hikita Eri、Gando Yoshito、Chubachi Hideo、Shirota Mikio、Kushiyama Akifumi、Yasu Takeo
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 17 Issue: 4 Pages: 289-293

    • DOI

      10.5582/ddt.2023.01043

    • ISSN
      1881-7831, 1881-784X
    • Year and Date
      2023-08-31
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plasma Cabozantinib Level Measurement in Patients with Renal Cell and Hepatocellular Carcinomas Using a Simple HPLC?UV Method Suitable for Clinical Application2023

    • Author(s)
      Yasu Takeo、Gando Yoshito、Nishijima Ryosuke、Ikuta Risa、Suzuki Motofumi、Shirota Mikio
    • Journal Title

      Current Oncology

      Volume: 30 Issue: 5 Pages: 4871-4879

    • DOI

      10.3390/curroncol30050367

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between plasma venetoclax trough levels and serum C-reactive protein levels in patients with acute myeloid leukemia treated with venetoclax plus azacitidine2023

    • Author(s)
      Yasu Takeo、Gando Yoshito、Shirota Mikio、Kosugi Nobuharu、Kobayashi Masayuki
    • Journal Title

      Leukemia & Lymphoma

      Volume: 65 Issue: 1 Pages: 128-131

    • DOI

      10.1080/10428194.2023.2264427

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Invasive Fungal Disease in Patients with Chronic Lymphocytic Leukemia in Japan: A Retrospective Database Study2022

    • Author(s)
      Yasu Takeo、Sakurai Kotono、Akazawa Manabu
    • Journal Title

      Current Oncology

      Volume: 29 Issue: 5 Pages: 3242-3251

    • DOI

      10.3390/curroncol29050264

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral azole antifungal prophylaxis in Japanese patients with chronic lymphocytic leukemia receiving ibrutinib: a nationwide cohort study2022

    • Author(s)
      Yasu Takeo、Sakurai Kotono、Hoshino Makoto、Akazawa Manabu
    • Journal Title

      Leukemia & Lymphoma

      Volume: 64 Issue: 3 Pages: 730-733

    • DOI

      10.1080/10428194.2022.2161305

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics of ibrutinib in a patient with chronic lymphocytic leukemia on hemodialysis2022

    • Author(s)
      Ohtani Toyoji、Tani Akiko、Namme Yuki、Namme Rie、Hirose Maki、Shingu Ikuo、Kizawa Yusuke、Endo Akira、Yasu Takeo
    • Journal Title

      Clinical Nephrology

      Volume: 98 Issue: 6 Pages: 301-304

    • DOI

      10.5414/cn110859

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] High-Performance Liquid Chromatography for Ultra-Simple Determination of Plasma Voriconazole Concentration2022

    • Author(s)
      Yasu Takeo、Nomura Yuka、Gando Yoshito、Matsumoto Yasuhiko、Sugita Takashi、Kosugi Nobuharu、Kobayashi Masayuki
    • Journal Title

      Journal of Fungi

      Volume: 8 Issue: 10 Pages: 1035-1035

    • DOI

      10.3390/jof8101035

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacokinetics of voriconazole and its alteration by Candida albicans infection in silkworms2021

    • Author(s)
      Yasu Takeo、Matsumoto Yasuhiko、Sugita Takashi
    • Journal Title

      The Journal of Antibiotics

      Volume: 74 Issue: 7 Pages: 443-449

    • DOI

      10.1038/s41429-021-00428-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] ベネトクラクス錠の破砕投与が血中濃度上昇に影響した1例2023

    • Author(s)
      丸藤 義翔 , 安 武夫 , 城田 幹夫 , 小林 真之
    • Organizer
      日本臨床腫瘍薬学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] カボザンチニブの血中濃度モニタリングを臨床応用するためのシンプルなHPLC-UVによる測定方法の確立2023

    • Author(s)
      丸藤 義翔, 安 武夫, 城田 幹生
    • Organizer
      第39回日本TDM学会・学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] HPLC-UVによるベネトクラクスの血中濃度測定系の確立2022

    • Author(s)
      丸藤義翔、野村有加、安 武夫
    • Organizer
      第32回 日本医療薬学会年会
    • Related Report
      2022 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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