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Clinical pharmacology study on drug-degrading esterase PON3, gene polymorphism and pharmacokinetic influence

Research Project

Project/Area Number 17K08949
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Watanabe Hiroshi  浜松医科大学, 医学部, 理事 (50262803)

Co-Investigator(Kenkyū-buntansha) 三坂 眞元  福島県立医科大学, 医学部, 講師 (10583635)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords臨床薬理学 / パラオキソナーゼ / シンバスタチン / 薬物動態 / 抗動脈硬化作用 / 遺伝的多型 / パロキソナーゼ3 / 民族差 / 動脈硬化 / 肥満 / パラオキソナーゼ(PON)3 / 遺伝子多型
Outline of Final Research Achievements

Paraoxonase 3 (PON3) possesses atheroprotective properties. Serum concentration of PON3 was 9.6 ± 3.8 μg / mL in Japanese, which was about 5 times higher than the reported value in Caucasian. Because the frequency of PON3 gene polymorphisms was relatively low, it was suggested that epigenetic factors might be involved in this ethnic difference in PON3 concentration. In addition, serum PON3 concentration showed a negative correlation with body weight and BMI, and a positive correlation with the metabolism of simvastatin to simvastatin acid..

Academic Significance and Societal Importance of the Research Achievements

本研究では抗動脈硬化作用が注目されるパラオキソナーゼ(PON)3に関する日本人の血清中PON3濃度、個人間変動要因、シンバスタチンの体内動態との関連、また日本人のPON3遺伝子多型と頻度について検討し、 PON3に関する日本人の基盤データを構築した。日本人の血清PON3濃度がコーカシアン系人種に比較し高く、動脈硬化や肥満との関連とともに、シンバスタチンの薬物動態の人種差要因となることを初めて示したものである。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (25 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (14 results) (of which Int'l Joint Research: 3 results) Book (6 results)

  • [Journal Article] Clinical Outcomes and Treatment Options in Patients With Pulmonary Hypertension Who Received Pulmonary Hypertension-Specific Drugs-Single-Center Case Series-2019

    • Author(s)
      Kamiya C, Odagiri K , Hakamata A, Inui N, Watanabe H
    • Journal Title

      Circulation Reports

      Volume: 1 Pages: 389-395

    • NAID

      130007705469

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transient Laterality of Cerebral Oxygenation Changes in Response to Head-of-Bed Manipulation in Acute Ischemic Stroke2019

    • Author(s)
      Katayama、Odagiri、Hakamata、Inui、Yamauchi、Watanabe
    • Journal Title

      Journal of Clinical Medicine

      Volume: 8 Issue: 10 Pages: 1739-1739

    • DOI

      10.3390/jcm8101739

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of rifampicin and clarithromycin on the CYP3A activity in patients with Mycobacterium avium complex,2019

    • Author(s)
      Akiyama N, Inui N, Mori K, Nakamura Y, Hayakawa H, Tanaka S, Uchida S, Namiki N, Watanabe H, Suda T,
    • Journal Title

      J Thorac Dis

      Volume: 11(9) Pages: 3814-3821

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 臨床研究法の現状における課題と運用改善に向けた提言:GCP・医学系指針及び海外制度との比較から-第1報 医薬品等の品質・安全性の確保-2019

    • Author(s)
      栗原千絵子,鈴木千恵子,小池竜司,佐藤弥生,渡邉裕司
    • Journal Title

      臨床評価

      Volume: 47(1) Pages: 127-152

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 薬と緑茶の相互作用2019

    • Author(s)
      三坂眞元
    • Journal Title

      機能性食品と薬理栄養

      Volume: 13(1) Pages: 35-43

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Impairment of cerebral blood flow autoregulation in patients with acute cerebral infarction recovered within 7-10 days after onset2019

    • Author(s)
      Katayama N,Odagiri K, Hakamata A,Inui N, Yamauchi K,Watanabe H
    • Organizer
      International Stroke Conference (AHA)2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Role of NO-sGC-cGMP axis in Pulmonary Arterial Hypertension2019

    • Author(s)
      Watanabe H
    • Organizer
      2019 TPHA-Autumn conference -PCPHS-TPHA Joint PH Forum
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 健常者におけるSelexipag とClopidogrel併用時の薬物動態について2019

    • Author(s)
      神谷千明,袴田晃央,片山直紀,乾直輝, 小田切圭一,田中紫茉子,内田信也,並木徳之,渡邉裕司
    • Organizer
      第4回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 成人肺高血圧患者における肺高血圧症治療薬の母集団薬物動態解析2019

    • Author(s)
      田中紫茉子,内田信也,中川篤毅,袴田晃央,神谷千明,小田切圭一,乾直輝,渡邉裕司,並木徳之
    • Organizer
      第4回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] ベラプロストをセレキシパグに変更したPAH患者での薬物濃度2019

    • Author(s)
      小田切圭一,神谷千明,袴田晃央,乾直輝,田中紫茉子,内田信也,渡邉裕司
    • Organizer
      第4回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 健常成人におけるシトクロムP4502C8阻害薬クロビドグレル併用時のセレキシパグの薬物動態について2019

    • Author(s)
      片山直紀,小田切圭一,神谷千明,袴田晃央,乾直輝,田中紫茉子,内田信也,渡邉裕司
    • Organizer
      第40回日本臨床薬理学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Influence of green tea on pharmacokinetics of fexofenadine in healthy volunteers2019

    • Author(s)
      Shingen Misaka, Yuko Ono, Tomoyuki Ono, Hiroshi Ogata, Kenju Shimomura
    • Organizer
      14th Congress of the European Association for Clinical Pharmacology and Therapeutics
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ナドロールの尿中排泄量を指標とするトランスポーターを介した薬物相互作用評価2019

    • Author(s)
      嶋崎 翔,和泉 啓司郎,下村 健寿,三坂 眞元
    • Organizer
      第40回日本臨床薬理学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 健常人において緑茶カテキンがフェキソフェナジンの体内動態に及ぼす影響2019

    • Author(s)
      三坂 眞元,大野 雄康,小野 委成,尾形 浩,下村 健寿
    • Organizer
      第3回日本臨床薬理学会北海道・東北地方会
    • Related Report
      2019 Research-status Report
  • [Presentation] Genotype-specific effects of cytochrome P450 inducers and inhibitors on CYP2C19 enzyme activity.2018

    • Author(s)
      Kamiya C,Watanabe H
    • Organizer
      第39回日本臨床薬理学会学術総会・WCP2018(ポスター)
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺高血圧症治療薬における薬物治療モニタリング(TDM)の検討2017

    • Author(s)
      内田信也,袴田晃央,田中紫茉子,神谷千明,石川貴充,小田切圭一,乾直輝,森善樹,並木徳之,渡邉裕司
    • Organizer
      第2回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 薬物増量にTDMを用いた肝・腎機能障害合併肺高血圧症の例2017

    • Author(s)
      袴田晃央,石川貴充,田中紫茉子,神谷千明,小田切圭一,内田信也,乾直輝,渡邉裕司
    • Organizer
      第2回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] cytochrome P450における遺伝子多型と酵素誘導/阻害の関連2017

    • Author(s)
      神谷千明,小田切圭一,宮川幸子,袴田晃央,乾直輝,田中紫茉子,内田信也,並木徳之,渡邉裕司
    • Organizer
      第38回日本臨床薬理学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 治療的薬物濃度モニタリング(TDM)を用いて薬剤調整を行った肝・腎機能障害合併肺高血圧症の1例2017

    • Author(s)
      袴田晃央,石川貴充,田中紫茉子,神谷千明,小田切圭一,内田信也,乾直輝,渡邉裕司
    • Organizer
      第38回日本臨床薬理学会学術総会
    • Related Report
      2017 Research-status Report
  • [Book] 今日の治療指針20202020

    • Author(s)
      越前宏俊、渡邉裕司
    • Total Pages
      2192
    • Publisher
      医学書院
    • ISBN
      9784260039390
    • Related Report
      2020 Annual Research Report
  • [Book] 今日の治療指針20192019

    • Author(s)
      越前宏俊、渡邉裕司
    • Publisher
      医学書院
    • Related Report
      2019 Research-status Report
  • [Book] 治療薬のデータブック2019

    • Author(s)
      渡邉裕司
    • Total Pages
      68
    • Publisher
      日本医事新報
    • Related Report
      2019 Research-status Report
  • [Book] 今日の治療指針20182018

    • Author(s)
      越前宏俊,渡邉裕司
    • Publisher
      医学書院
    • Related Report
      2018 Research-status Report
  • [Book] 今日の治療指針 2年版[ポケット判]2017

    • Author(s)
      越前宏俊,渡邉裕司
    • Publisher
      医学書院
    • Related Report
      2017 Research-status Report
  • [Book] 内科学 第11版2017

    • Author(s)
      渡邉裕司
    • Publisher
      朝倉書店
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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