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2017 Fiscal Year Annual Research Report

Optimization of antimicrobial therapy based on relation and interaction among drug, causative organism and host immunity

Research Project

Project/Area Number 15K08590
Research InstitutionHiroshima University

Principal Investigator

猪川 和朗  広島大学, 医歯薬保健学研究科(薬), 准教授 (40363048)

Co-Investigator(Kenkyū-buntansha) 森川 則文  広島大学, 医歯薬保健学研究科(薬), 教授 (30346481)
大毛 宏喜  広島大学, 病院(医), 教授 (70379874)
Project Period (FY) 2015-04-01 – 2018-03-31
Keywords臨床 / 感染症 / 薬物動態 / 薬力学
Outline of Annual Research Achievements

本研究では,感染症治療における薬物[抗菌薬・抗真菌薬・抗ウイルス薬]-病原体[細菌・真菌・ウイルス]-宿主[患者]免疫の3者が,相互に関連し合う関係性を解明し,薬物治療法を定量的に最適化することを目的とした。平成29年度には,下記のとおり実施した。
薬物動態・病原体耐性・宿主免疫データの収集に関しては,β-ラクタム系抗菌薬(cefepime,flomoxef,imipenem,piperacillin-tazobactam,sulbactam),キノロン系抗菌薬(levofloxacin,pazufloxacin,sitafloxacin),アミノグリコシド系抗菌薬(amikacin,arbekacin),抗耐性菌薬linezolid,teicoplanin,抗真菌薬voriconazoleの血漿中および組織体液(腹水・腹膜・前立腺・精巣上体)中の薬物濃度を測定した。微生物学的試験や殺菌時間曲線試験のデータ,また各種の臨床データを収集することができた。
定量的な解析・予測に関しては,薬物動態データおよび基礎・非臨床や治療データを定量的に評価し,母集団pharmacokinetic-pharmacodynamicモデリングおよびMonte Carloランダムシミュレーションなどの手法により,様々な関連性を説明し表現する関係式を構築することができた。
感染患者への臨床適用と修正に関しては,薬物,病原体,宿主の特性因子などから,個別最適療法を設計するツールを開発した。そして,患者への臨床適用し,医療現場から適用結果のフィードバックを得ることができた。

  • Research Products

    (15 results)

All 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (10 results) (of which Int'l Joint Research: 8 results)

  • [Journal Article] Population pharmacokinetics/pharmacodynamics of linezolid in sepsis patients with and without continuous renal replacement therapy.2018

    • Author(s)
      Ide Takeshi, Takesue Yoshio, Ikawa Kazuro, Morikawa Norifumi, Ueda Takashi, Takahashi Yoshiko, Nakajima Kazuhiko, Takeda Kenta, Nishi Shinichi.
    • Journal Title

      Int J Antimicrob Agents.

      Volume: in press Pages: in press

    • DOI

      10.1016/j.ijantimicag.2018.01.021

    • Peer Reviewed
  • [Journal Article] Pharmacokinetics and outcome of tazobactam/piperacillin in Japanese patients undergoing low-flow continuous renal replacement therapy: dosage considerations.2017

    • Author(s)
      Kohama Hanako, Ide Takeshi, Ikawa Kazuro, Morikawa Norifumi, Nishi Shinichi.
    • Journal Title

      Clin Pharmacol.

      Volume: Volume 9 Pages: 39~44

    • DOI

      10.2147/CPAA.S127502

    • Peer Reviewed
  • [Journal Article] Clinical pharmacokinetics of oral levofloxacin and sitafloxacin in epididymal tissue.2017

    • Author(s)
      Sadahira Takuya, Wada Koichiro, Ikawa Kazuro, Morikawa Norifumi, Kurahashi Hiroaki, Yoshioka Takashi, Ariyoshi Yuichi, Kobayashi Yasuyuki, Araki Motoo, Ishii Ayano, Watanabe Masami, Uehara Shinya, Watanabe Toyohiko, Nasu Yasutomo.
    • Journal Title

      J Infect Chemother.

      Volume: 23 Pages: 214~217

    • DOI

      10.1016/j.jiac.2016.12.010

    • Peer Reviewed
  • [Journal Article] Pharmacokinetics of piperacillin-tazobactam in plasma, peritoneal fluid and peritoneum of surgery patients, and dosing considerations based on site-specific pharmacodynamic target attainment.2017

    • Author(s)
      Murao Naoki, Ohge Hiroki, Ikawa Kazuro, Watadani Yusuke, Uegami Shinnosuke, Shigemoto Norifumi, Shimada Norimitsu, Yano Raita, Kajihara Toshiki, Uemura Kenichiro, Murakami Yoshiaki, Morikawa Norifumi, Sueda Taijiro.
    • Journal Title

      Int J Antimicrob Agents.

      Volume: 50 Pages: 393~398

    • DOI

      10.1016/j.ijantimicag.2017.03.025

    • Peer Reviewed
  • [Journal Article] Clinical pharmacokinetics and pharmacodynamic target attainment of pazufloxacin in prostate tissue: Dosing considerations for prostatitis.2017

    • Author(s)
      Nakamura Kogenta, Ikawa Kazuro, Nishikawa Genya, Kobayashi Ikuo, Narushima Masahiro, Muramatsu Hiroyuki, Morinaga Shingo, Kajikawa Keishi, Kato Yoshiharu, Watanabe Masahito, Zennami Kenji, Kanao Kent, Morikawa Norifumi, Sumitomo Makoto.
    • Journal Title

      J Infect Chemother.

      Volume: 23 Pages: 809~813

    • DOI

      10.1016/j.jiac.2017.08.005

    • Peer Reviewed
  • [Presentation] Population pharmacokinetic-pharmacodynamic modeling and simulation of imipenem for dosing optimization in pediatric patients.2017

    • Author(s)
      Ikawa K, Morikawa N.
    • Organizer
      15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
    • Int'l Joint Research
  • [Presentation] Prediction of thrombocytopenia associated with linezolid based on pharmacokinetic-pharmacodynamic simulation.2017

    • Author(s)
      Onita T, Ishihara N, Nishimura N, Tamaki H, Ikawa K, Morikawa N, Naora K.
    • Organizer
      15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
    • Int'l Joint Research
  • [Presentation] Population pharmacokinetic analysis of piperacillin and tazobactam by using their blood and urine level data in Japanese pediatric patients.2017

    • Author(s)
      Ishihara N, Nishimura N, Ikawa K, Tamaki H, Morikawa N, Naora K.
    • Organizer
      15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
    • Int'l Joint Research
  • [Presentation] Voriconazole TDM based on both unchanged drug and metabolite concentrations in Japanese patients.2017

    • Author(s)
      Shigemi A, Watanabe E, Umezaki Y, Ikeda R, Matsumoto K, Yokoyama Y, Ikawa K, Morikawa N, Takeda Y.
    • Organizer
      15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
    • Int'l Joint Research
  • [Presentation] External evaluation of amikacin population pharmacokinetic models in Japanese adult patients.2017

    • Author(s)
      Sako K, Yoshikawa N, Hashimoto N, Matsuki Y, Arai K, Ikawa K, Morikawa N, Matsuda Y.
    • Organizer
      15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
    • Int'l Joint Research
  • [Presentation] Estimation of the duration to reach peak arbekacin concentration by Monte Carlo simulation.2017

    • Author(s)
      Yamaguchi K, Abe T, Takeuchi T, Watanabe M, Tsuchiya K, Ikawa K, Fukuoka N, Kaji M, Tanaka H, Asakura M, Kosaka S, Houchi H.
    • Organizer
      15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
    • Int'l Joint Research
  • [Presentation] Pharmacokinetic and pharmacodynamic characterization of piperacillin-tazobactam, flomoxef and pazufloxacin in prostate tissue and plasma of prostatic hypertrophy patients.2017

    • Author(s)
      Kuroda A, Ikawa K, Ugawa H, Tanaka K, Odagawa S, Matsuyama Y, Nakamura K, Nishikawa G, Kobayashi I, Sumitomo M, Morikawa N.
    • Organizer
      15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
    • Int'l Joint Research
  • [Presentation] Pharmacokinetic/pharmacodynamic evaluation of teicoplanin against Staphylococcus aureus in murine thigh infection model.2017

    • Author(s)
      Takeda Y, Watanabe E, Shigemi A, Umezaki Y, Nakamura K, Ueno K, Ikeda R, Yokoyama Y, Matsumoto K, Ikawa K, Morikawa N.
    • Organizer
      15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
    • Int'l Joint Research
  • [Presentation] Semi-mechanistic pharmacokinetic/pharmacodynamic modeling and simulation for time-kill curve profile of sulbactam against Acinetobacter baumannii.2017

    • Author(s)
      Yokoyama Y, Ikawa K, Matsumoto K, Nakamura T, Morikawa N.
    • Organizer
      第11回次世代を担う若手医療薬科学シンポジウム
  • [Presentation] セフェピム投与後に代謝性脳症を発現し薬物血中濃度を測定した1例.2017

    • Author(s)
      眞継賢一, 猪川和朗, 森川則文, 濱口良彦.
    • Organizer
      第65回日本化学療法学会学術集会・第91回日本感染症学会学術講演会

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Published: 2018-12-17  

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