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Exploration of enantiomers which is clinically applicable to the pharmacotherapy of depressive disorders by population pharmacokinetic analysis

Research Project

Project/Area Number 17K10280
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionDokkyo Medical University

Principal Investigator

SHIMODA KAZUTAKA  獨協医科大学, 医学部, 教授 (30196555)

Co-Investigator(Kenkyū-buntansha) 渡邊 崇  獨協医科大学, 医学部, 講師 (10621451)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordspharmacokinetics / pharmacogenetics / enantiomer / venlafaxine / mirtazapine / CYP2D6 / enatiomer / エナンチオマー
Outline of Final Research Achievements

The pharmacokinetics of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV) were investigated. The correlation coefficients between dose of VEN and plasma concentration of VEN and ODV were 0.57 and 0.94, respectively. Addtionally, the effect of CYP2D6 gene polymorphism on the plasma levels of VEN, ODV and each enantiomer (S-VEN, R-VEN, S-OD, R-ODV) was evaluated. The plasma concentration of each enantiomer was significantly correlated with the dose of VEN. Corrected VEN, ODV, S-ODV, and R-ODV plasma concentrations showed a significant correlation with age. Neither plasma concentration of each enantiomer was significantly associated with the number of CYP2D6*10 alleles.

Academic Significance and Societal Importance of the Research Achievements

現在、モノアミン仮説を凌駕するような革新的な抗うつ薬の開発は停滞しているといって差し支えない。現在使用されているベンラファキシンやミルタザピンのエナンチオマーの薬物動態を解析することによって、新規抗うつ薬の有効性に寄与している物質の同定を行い副作用のリスクが少ない物質を抽出することが期待され、短期間で比較的安全かつ効率的なプロセスで新しい抗うつ薬をうつ病患者に供給することができる可能性が示された。

Report

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

    (17 results)

All 2020 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (14 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [Journal Article] 8-Hydroxylation and Glucuronidation of Mirtazapine in Japanese Psychiatric Patients: Significance of the Glucuronidation Pathway of 8-Hydroxy-Mirtazapine2019

    • Author(s)
      Shinozaki Masataka、Pierce Jason、Hayashi Yuki、Watanabe Takashi、Sasaki Taro、Komahashi-Sasaki Hazuki、Akiyama Kazufumi、Kato Kazuko、Inoue Yoshimasa、Tsuchimine Shoko、Yasui-Furukori Norio、Ozeki Yuji、Shimoda Kazutaka
    • Journal Title

      Pharmacopsychiatry

      Volume: 52 Issue: 05 Pages: 237-244

    • DOI

      10.1055/a-0918-6408

    • NAID

      130007811500

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of the Proarrhythmic Effects of Antidepressants according to QT Interval, QT Dispersion and T Wave Peak-to-End Interval in the Clinical Setting2019

    • Author(s)
      Hiroaki Okayasu, Yuji Ozeki, Kumiko Fujii, Yumiko Takano, Takahiro Shinozaki, Masami Ohrui, and Kazutaka Shimoda
    • Journal Title

      Psychiatry Investigation

      Volume: 16(2): Issue: 2 Pages: 159-166

    • DOI

      10.30773/pi.2018.12.11

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early improvement and marriage are determinants of the 12-month treatment outcome of paroxetine in outpatients with panic disorder2017

    • Author(s)
      Watanabe T, Ueda M, Ishiguro S, Hayashi Y, Aoki A, Shinozaki M, Kato K, Akiyama K, Shimoda K
    • Journal Title

      Clinical Psychopharmacology and Neuroscience

      Volume: 15 Issue: 4 Pages: 382-390

    • DOI

      10.9758/cpn.2017.15.4.382

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 日本人精神疾患患者におけるmirtazapineの水酸化とグルクロン酸抱合:8-OH-mirtazapineのグルクロン酸抱合経路の意義2020

    • Author(s)
      篠﨑 將貴、ピアス ジェイソン、林 有希、渡邊 崇、佐々木 太郎、佐々木 はづき、秋山 一文、加藤 和子、井上 義政、土嶺 章子、古郡 規雄、尾関 祐二、下田 和孝
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 日本人患者におけるCYP2D6遺伝子多型がVenlafaxineおよびその代謝物の薬物動態に及ぼす影響について2020

    • Author(s)
      佐々木 はづき、渡邊 崇、井上 義政、佐々木 太郎、篠﨑 將貴、林 有希、加藤 和子、黒田 仁一、古郡 規雄、下田 和孝
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Effects of CYP2D6 polymorphism on enetiomeric metabolism of venlafaxine and O-desmethylvenlafaxine in Japanese pstients2019

    • Author(s)
      Taro Sasaki, Takashi Watanabe, Hazuki Sasaki, Masataka Shinozaki, Akiko Aoki, Yuki Hayashi, Kazuko Kato, Jinichi Kuroda, Norio Furukori, Kazutaka Shimoda
    • Organizer
      6th Asian College of Neuropsychopharmacology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 8-Hydroxylation and glucuronidation of mirtazapine in Japanese psychiatric patients: Significance of the glucuronidation pathway of 8-hydroxy-mirtazapine.2019

    • Author(s)
      Masataka Shinozaki, Jason Pierce1, Yuki Hayashi, Takashi Watanabe, Taro Sasaki, Hazuki Komahashi-Sasaki, Kazufumi Akiyama, Kazuko Kato,Yoshimasa Inoue, Shoko Tsuchimine, Norio Yasui-Furukori, Yuji Ozeki, Kazutaka Shimoda
    • Organizer
      The 7th China-Japan joint meeting of basic and clinical pharmacology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 8-Hydroxylation and glucuronidation of mirtazapine in Japanese psychiatric patients: Significance of the glucuronidation pathway of 8-hydroxy-mirtazapine2019

    • Author(s)
      Hazuki Komahashi-Sasaki, Takashi Watanabe, Yoshimasa Inoue, Taro Sasaki, Masataka Shinozaki, Yuki Hayashi, Kazuko Kato, Jinichi Kuroda, Norio Yasui-Furukori, Kazutaka Shimoda
    • Organizer
      32nd Annual meeting og European College of Neuropsychopharmacology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Early improvement and marriage are determinants of 1-year treatment outcome of paroxetine in outpatients with panic disorder2018

    • Author(s)
      Takashi Watanabe, Mikito Ueda, Shin Ishiguro, Yuki hayashi, Akiko Ariyoshi, Masataka Shinozaki, Kazuko Kato, Kazufumi Akiyama, Kazutaka Shimoda
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology. July 1-6, 2018, Kyoto.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 日本人におけるvenlafaxine と活性代謝産物の血中濃度に基づいた薬物動態学的解析2018

    • Author(s)
      駒橋はづき、渡邊、崇、井上義政、佐々木太郎、篠﨑將貴、有吉顕子、林 有希、加藤和子、黒田仁一、古郡規雄、下田和孝
    • Organizer
      第35回日本TDM 学会学術大会、福岡、2018年5月26日、27日
    • Related Report
      2018 Research-status Report
  • [Presentation] VenlafaxineおよびO-desmethylvenlafaxineの鏡像異性体の薬物動態学的解析2018

    • Author(s)
      佐々木太郎、渡邊 崇、井上義政、駒橋はづき、篠崎將貴、青木顕子、林 有希、加藤和子、黒田仁一、古郡規雄、下田和孝
    • Organizer
      第28回日本臨床精神神経薬理学会・第48回日本神経精神薬理学会合同年会、2018年11月14日―16日、東京
    • Related Report
      2018 Research-status Report
  • [Presentation] ノルトリプチリン・パロキセチンによって薬剤性抗利尿ホルモン不適合分泌症候群が惹起されたうつ病患者に対するミアンセリンの有用性2018

    • Author(s)
      石井沙安也、岡安寛明、藤井久彌子、尾関祐二、加瀬正人、麻生好正、下田和孝
    • Organizer
      第28回日本臨床精神神経薬理学会・第48回日本神経精神薬理学会合同年会、2018年11月14日―16日、東京
    • Related Report
      2018 Research-status Report
  • [Presentation] VenlafaxineおよびO-desmethylvenlafaxineの鏡像異性体の薬物動態学的解析2018

    • Author(s)
      駒橋はづき、渡邊 崇、井上義政、佐々木太郎、篠崎將貴、青木顕子、林 有希、加藤和子、黒田仁一、下田和孝
    • Organizer
      第3回日本臨床薬理学会関東甲信越地方会、2018年11月24-24日、横浜
    • Related Report
      2018 Research-status Report
  • [Presentation] Pharmacokinetics of mirtazapine included glucuronidated metabolites in Japanese psychiatric patients2017

    • Author(s)
      Takashi Watanabe, Yoshimasa Inoue, Yuki Hayashi, Jason Pierce, Akiko Aoki, Shin Ishiguro, Mikito Ueda, Kazufumi Akiyama, Shoko Tsuchimine, Norio Yasui-Furukori, Kazutaka Shimoda
    • Organizer
      5th Asian College of Neuropsychopharmacology,
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 日本人におけるvenlafaxineの薬物動態学的解析2017

    • Author(s)
      篠崎將貴、渡邊 崇、井上義政、有吉顕子、林 有希、加藤和子、黒田仁一、下田和孝
    • Organizer
      第27回日本臨床精神神経薬理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 抗うつ薬パロキセチンの血中濃度と治療効果に関する母集団薬物動態―薬力学解析2017

    • Author(s)
      岩下知磨、宮田 哲、上田幹人、猿渡淳二、青木顕子、西村美紀、土嶺章子、鬼木健太郎、下田和孝、古群規雄
    • Organizer
      第27回日本臨床精神神経薬理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 日本人患者を対象としたvenlafaxineとその活性代謝産物の薬動態学的解析2017

    • Author(s)
      渡邊 崇、井上義政、篠崎將貴、林 有希、有吉顕子、加藤和子、黒田仁一、秋山一文、下田和孝
    • Organizer
      第38回日本臨床薬理学会学術総会
    • Related Report
      2017 Research-status Report

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

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