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Investigation of interindividual variability in pharmacokinetics of and clinical responses to neuropathic pain medications in cancer patients

Research Project

Project/Area Number 18K06746
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Kawakami Junichi  浜松医科大学, 医学部附属病院, 教授 (50272539)

Co-Investigator(Kenkyū-buntansha) 内藤 隆文  浜松医科大学, 医学部附属病院, 特任准教授 (80422749)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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)
Keywords神経障害性疼痛 / バイオマーカー / 薬物動態 / 炎症性サイトカイン / がん性疼痛 / デュロキセチン / プレガバリン / 神経障害性疼痛治療薬 / がん悪液質 / 個別化薬物療法
Outline of Final Research Achievements

Cancer patients have a large variation in clinical responses to analgesic drugs for neuropathic pain. The variation is partially associated with the individual pharmacokinetics of analgesic drugs for neuropathic pain under the cancer states. In addition, cancer cachexia and drug-drug interaction also potentially affect the variations in pharmacokinetics and adverse effects of analgesic drugs for neuropathic pain. This study evaluated the predictability of the pharmacokinetics of pregabalin and duloxetine and central nervous system symptoms in cancer patients. Plasma pregabalin was altered with renal function, systemic inflammation status, and opioid analgesic co-treatment. The incidence of central nervous system symptoms observed in cancer patients was more related to cachexia progression and opioid analgesic co-treatment than to altered pregabalin concentration. Duloxetine has a large interindividual variation in plasma concentration regardless of the affection of a cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究では、がん患者における神経障害性疼痛治療薬の体内動態や中枢性有害作用の個人差を規定する要因が明らかになった。このことの学術的意義として、オピオイド系鎮痛薬などの併用薬や腎機能などの患者情報とともに、がん悪液質などのがん進行に伴う炎症度の評価が、がん患者ごとの神経障害性疼痛治療薬の体内動態や中枢性有害作用の予測に繋がる。
本研究成果の社会的意義として、がん患者における神経障害性疼痛治療薬の体内動態や中枢性有害作用の予測は、神経障害性疼痛治療薬の忍容性を向上させるとともに、オピオイド系鎮痛薬を併用したがん性疼痛緩和療法におけるがん患者のQOLの向上が期待できる。

Report

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

    (3 results)

All 2021 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results)

  • [Journal Article] Impact of cachexia and opioid analgesic co-treatment on pregabalin pharmacokinetics and central nervous system symptoms in cancer patients.2019

    • Author(s)
      Nozomi Yoshikawa, Takafumi Naito, Tatsuya Yagi, and Junichi Kawakami
    • Journal Title

      Therapeutic Drug Monitoring

      Volume: 41 Issue: 5 Pages: 591-597

    • DOI

      10.1097/ftd.0000000000000634

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] がん患者におけるオピオイド系鎮痛薬の体内動態および臨床効果に及ぼす遺伝的要因2021

    • Author(s)
      内藤隆文
    • Organizer
      第14回日本緩和医療薬学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] デュロキセチン服用妊婦における臍帯血・母体血中薬物濃度と新生児薬物離脱症候群との関係2020

    • Author(s)
      田口怜奈, 内藤隆文, 鈴木光路, 伊東宏晃, 川上純一
    • Organizer
      第30回日本医療薬学会年会
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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