並列タイトル等がん患者におけるプレガバリンの薬物動態と中枢神経症状に対する悪液質とオピオイド鎮痛薬併用の影響
タイトル（掲載誌）Therapeutic drug monitoring
一般注記doctoral
医学系研究科
BACKGROUND: Cancer patients receiving pregabalin potentially have a high incidence of central nervous system (CNS) symptoms. The purpose of this study was to explore clinical factors influencing the incidence of CNS symptoms, including plasma pregabalin exposure, cancer cachexia, and opioid analgesic co-treatment.METHODS: Sixty-eight cancer patients receiving twice-daily pregabalin were enrolled. Plasma concentrations of pregabalin, clinical laboratory data, opioid analgesic co-treatment, and the Glasgow Prognostic Score (GPS), which is an inflammation-based cachexia score, were considered as clinical factors. The incidence of CNS symptoms was collected from the patients’ medical records. The pre-dose plasma concentrations of pregabalin at steady-state was determined by ultra-high-performance liquid chromatography.RESULTS: The steady-state trough plasma pregabalin concentrations showed a large variability with an interquartile range of 0.43-1.2 mg/L per mg/kg and was negatively correlated with estimated glomerular filtration rate (eGFR). C-reactive protein (standardized partial regression coefficient, β=0.31) and opioid analgesic co-treatment (β=0.24) were also identified in addition to eGFR (β=-0.60) in the multiple regression analysis. The incidence of CNS symptoms was significantly increased with opioid analgesic co-treatment and a higher GPS but not with the absolute value of plasma pregabalin concentrations, eGFR, nor other clinical laboratory data.CONCLUSIONS: In cancer patients, steady-state trough plasma pregabalin concentrations were altered with renal function, systemic inflammation, and opioid analgesic co-treatment. However, a higher incidence of CNS symptoms observed in cancer patients on pregabalin was more related to cachexia and opioid analgesic co-treatment than to altered pregabalin concentrations.
DOIinfo:doi/10.1097/FTD.0000000000000634
コレクション（個別）国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
受理日（W3CDTF）2021-05-20T03:24:30+09:00
連携機関・データベース国立国会図書館 : 国立国会図書館デジタルコレクション