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New anti-MRSA drug optimal treatment strategy with Physiologically-based Pharmacokinetics/ Pharmacodynamics

Research Project

Project/Area Number 19K08950
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionUniversity of Toyama

Principal Investigator

YAMAMOTO Yoshihiro  富山大学, 学術研究部医学系, 教授 (70452844)

Co-Investigator(Kenkyū-buntansha) 辻 泰弘  日本大学, 薬学部, 教授 (20644339)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords抗菌薬適正使用 / 抗MRSA薬 / 薬物濃度 / 抗菌薬投与設計 / 特殊病態患者 / 生理学的薬物動態/薬力学モデル / 抗MRSA薬
Outline of Research at the Start

メチシリン耐性黄色ブドウ球菌 (MRSA)はわが国において依然として最も分離頻度が高い薬剤耐性菌である。しかし現在使用可能な抗MRSA薬はわずか6種類である。今回、『生理学的薬物動態/薬力学モデル (PBPK/PD)』を応用し、抗MRSA薬の個別化最適治療法を確立する。
本研究で開発する抗菌薬投与設計ソフトウェアは抗MRSA薬を使用する全ての施設で利用可能な血中および組織中濃度を予測できるソフトウェアであり、抗MRSA薬の適正使用につながり、ひいては薬剤耐性(Antimicrobial Resistance: AMR)感染症の減少に貢献できる。

Outline of Final Research Achievements

The objective of this study was to perform an external evaluation of linezolid population pharmacokinetic and pharmacodynamic models, to evaluate the predictive performance using an independent data set. Another aim was to offer an elegant environment for display and simulation of both the concentration and platelet count after linezolid administration.
We confirmed the transferability of population pharmacokinetic and pharmacodynamic models and also introduced application software based on our model for the therapeutic drug monitoring of linezolid.

Academic Significance and Societal Importance of the Research Achievements

MRSA感染症患者に対して、特殊病態別にプロスペクティブに適用することが初めて可能となった。本研究で開発した抗菌薬投与設計ソフトウェアは抗MRSA薬を使用する全ての施設で利用可能な血中および組織中濃度を予測できるソフトウェアであり、抗MRSA薬の適正使用につながり、ひいては薬剤耐性(Antimicrobial Resistance: AMR)感染症の減少に貢献できると考えている。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report

Research Products

(23 results)

All 2021 2020 2019

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (13 results)

  • [Journal Article] Proposal of initial and maintenance dosing regimens with linezolid for renal impairment patients2021

    • Author(s)
      Kawasuji Hitoshi、Tsuji Yasuhiro、Ogami Chika、Kimoto Kou、Ueno Akitoshi、Miyajima Yuki、Kawago Koyomi、Sakamaki Ippei、Yamamoto Yoshihiro
    • Journal Title

      BMC Pharmacology and Toxicology

      Volume: 22

    • DOI

      10.1186/s40360-021-00479-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Initially Reduced Linezolid Dosing Regimen to Prevent Thrombocytopenia in Hemodialysis Patients2021

    • Author(s)
      Kawasuji Hitoshi、Tsuji Yasuhiro、Ogami Chika、Kaneda Makito、Murai Yushi、Kimoto Kou、Ueno Akitoshi、Miyajima Yuki、Fukui Yasutaka、Sakamaki Ippei、Yamamoto Yoshihiro
    • Journal Title

      Antibiotics

      Volume: 10 Pages: 496-496

    • DOI

      10.3390/antibiotics10050496

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] External Evaluation of Population Pharmacokinetics and Pharmacodynamics in Linezolid-Induced Thrombocytopenia: The Transferability of Published Models to Different Hospitalized Patients2021

    • Author(s)
      Ogami Chika、Tsuji Yasuhiro、Nishi Yoshifumi、Kawasuji Hitoshi、To Hideto、Yamamoto Yoshihiro
    • Journal Title

      Therapeutic Drug Monitoring

      Volume: 43 Pages: 271-278

    • DOI

      10.1097/ftd.0000000000000816

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Classification Tree Analysis Based On Machine Learning for Predicting Linezolid-Induced Thrombocytopenia2021

    • Author(s)
      Takahashi Saki、Tsuji Yasuhiro、Kasai Hidefumi、Ogami Chika、Kawasuji Hitoshi、Yamamoto Yoshihiro、To Hideto
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: - Pages: 2295-2300

    • DOI

      10.1016/j.xphs.2021.02.014

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a simple method for measuring tedizolid concentration in human serum using HPLC with a fluorescent detector2021

    • Author(s)
      Tsuji Yasuhiro、Numajiri Miki、Ogami Chika、Kurosaki Fumihiro、Miyamoto Aoi、Aoyama Takahiko、Kawasuji Hitoshi、Nagaoka Kentaro、Matsumoto Yoshiaki、To Hideto、Yamamoto Yoshihiro
    • Journal Title

      Medicine

      Volume: 100

    • DOI

      10.1097/md.0000000000028127

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the relationship between linezolid exposure and hyponatremia2021

    • Author(s)
      Nishi Yoshifumi、Ogami Chika、Tsuji Yasuhiro、Kawasuji Hitoshi、Yamada Harumi、Kawai Shin、Sakamaki Ippei、To Hideto、Yamamoto Yoshihiro
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 27 Pages: 165-171

    • DOI

      10.1016/j.jiac.2020.08.017

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Positive infectious disease consultation at the time of blood culture collection is assosiated with decreased mortality in patients with methicillin-resistant Staphylococcus aureus bacteremia: A retrospective cohort study.2020

    • Author(s)
      Kawasuji H, Sakamaki I, Kawamura T, Ueno A, Miyajima Y, Matsumoto K, Kawago K, Higashi Y, Yamamoto Y.
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: - Pages: 588-595

    • DOI

      10.1016/j.jiac.2020.01.017

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacokinetics and pharmacodynamics of daptomycin in a clinical setting2020

    • Author(s)
      Tsukada Hiroko、Tsuji Yasuhiro、Yamashina Takuya、Tsuruta Minako、Hiraki Yoichi、Tsuruyama Moeko、Ogami Chika、Kawasuji Hitoshi、Sakamaki Ippei、Yamamoto Yoshihiro
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 26 Pages: 230-235

    • DOI

      10.1016/j.jiac.2019.08.017

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics, toxicity and clinical efficacy of linezolid in Japanese pediatric patients2019

    • Author(s)
      Ogami Chika、Tsuji Yasuhiro、To Hideto、Yamamoto Yoshihiro
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 25 Pages: 979-986

    • DOI

      10.1016/j.jiac.2019.05.025

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of a rifampicin pre-treatment on linezolid pharmacokinetics2019

    • Author(s)
      Okazaki Fumiyasu、Tsuji Yasuhiro、Seto Yoshihiro、Ogami Chika、Yamamoto Yoshihiro、To Hideto
    • Journal Title

      PLOS ONE

      Volume: 14

    • DOI

      10.1371/journal.pone.0214037

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 非透析腎機能障害者におけるリネゾリド初期投与量および維持投与量の検討2021

    • Author(s)
      川筋仁史,辻 泰弘,安河内励,竹腰雄祐,兼田磨熙杜,上野亨敏,宮嶋友希,河合暦美, 酒巻一平,山本善裕
    • Organizer
      第69回日本化学療法学会西日本支部総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 簡便かつ低濃度域まで測定可能なテジゾリド薬物濃度定量法の開発2021

    • Author(s)
      辻 泰弘,尾上知佳,川筋仁史,長岡健太郎,山本善裕
    • Organizer
      第68回日本化学療法学会東日本支部総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] リネゾリド個別化治療に向けたearly-TDMの必要性~機械学習による目標濃度・治療介入日の探索~2021

    • Author(s)
      辻 泰弘,高橋早紀,尾上知佳,川筋仁史,長岡健太郎,藤 秀人,山本善裕
    • Organizer
      MRSAフォーラム2020 in OSAKA
    • Related Report
      2021 Annual Research Report
  • [Presentation] 腎機能障害者におけるリネゾリド初期投与および維持投与量の検討2021

    • Author(s)
      川筋仁史,安河内励,辻 泰弘,尾上知佳,竹腰雄祐,兼田磨熙杜,村井佑至,木本 鴻,上野亨敏,宮嶋友希,河合暦美, 福井康貴,酒巻一平,山本善裕
    • Organizer
      MRSAフォーラム2020 in OSAKA
    • Related Report
      2021 Annual Research Report
  • [Presentation] 低ナトリウム血症におけるリネゾリドの暴露と患者背景の関連性の評価2021

    • Author(s)
      西 圭史,辻 泰弘,尾上知佳,吉田博昭,倉井大輔,河合 伸,川筋仁史、山本善裕
    • Organizer
      第95回日本感染症学会学術講演会・第69回日本化学療法学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 教育講演「わかりやすい抗MRSA薬の使い方」2020

    • Author(s)
      山本善裕
    • Organizer
      第68回日本化学療法学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 腎機能障害者におけるリネゾリド初期投与量の検討2020

    • Author(s)
      川筋仁史,辻 泰弘,上野亨敏,宮嶋友希,河合暦美,酒巻一平,山本善裕
    • Organizer
      第68回日本化学療法学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 非透析腎機能障害者におけるリネゾリド初期投与量および維持投与量の検討2020

    • Author(s)
      川筋仁史,辻 泰弘,安河内励,竹腰雄祐,兼田磨熙杜,上野亨敏,宮嶋友希,河合暦美, 酒巻一平,山本善裕
    • Organizer
      第68回日本化学療法学会西日本支部総会
    • Related Report
      2020 Research-status Report
  • [Presentation] リネゾリドPK/PDモデルの外部評価および投与設計支援ソフトウェアPycsimの開発2020

    • Author(s)
      尾上知佳,辻 泰弘,西 圭史,山本善裕
    • Organizer
      第67回日本化学療法学会東日本支部総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 抗MRSA薬の位置づけと使い分け「対オキサゾリジノン系派」2019

    • Author(s)
      山本善裕
    • Organizer
      MRSAフォーラム2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 機械学習とModel Based Exposure-Response解析によるリネゾリド誘発性血小板減少予測モデルの検討2019

    • Author(s)
      川村早紀,辻 泰弘,尾上知佳,中館成河,松本宣明,藤 秀人,山本善裕
    • Organizer
      第40回日本臨床薬理学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗MRSA薬TDM支援ソフトMr. TDMの開発2019

    • Author(s)
      酒巻一平,川村隆之,川筋仁史,宮嶋友希,河合暦美, 辻 泰弘, 山本善裕
    • Organizer
      第67回日本化学療法学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] MRSA菌血症診療におけるActive Consultationの有用性の検討2019

    • Author(s)
      川筋仁史,上野亨敏,宮嶋友希,河合暦美, 酒巻一平,山本善裕
    • Organizer
      第62回日本感染症学会中日本地方会学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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