2020 Fiscal Year Final Research Report

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

Research Project

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Project/Area Number	18K06746
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 47060:Clinical pharmacy-related
Research Institution	Hamamatsu 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
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
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.
Free Research Field	医療薬学、臨床薬理学、薬物動態学
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。