Impact of cachexia and opioid analgesic co-treatment on pregabalin pharmacokinetics and central nervous system symptoms in cancer patients.
Impact of cachexia and opioid analgesic co-treatment on pregabalin pharmacokinetics and central nervous system symptoms in cancer patients.
复制标题
恶病质和阿片类镇痛药联合治疗对癌症患者普瑞巴林药代动力学和中枢神经系统症状的影响。
DOI：
10.1097/ftd.0000000000000634
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发表时间：
2019
影响因子：
2.5
通讯作者：
and Junichi Kawakami
中科院分区：
文献类型：
--
作者：
Nozomi Yoshikawa;Takafumi Naito;Tatsuya Yagi;and Junichi Kawakami
背景：接受普瑞巴林治疗的癌症患者可能有较高的中枢神经系统（CNS）症状发生率。本研究的目的是探讨影响中枢神经系统症状发生率的临床因素，包括血浆普瑞巴林暴露，癌症恶病质，阿片类镇痛cotreatment.Methods：68例癌症患者接受每日两次普瑞巴林入组。普瑞巴林的血浆浓度、临床实验室数据、阿片类镇痛药联合治疗和格拉斯哥预后评分（一种基于炎症的恶病质评分）被视为临床因素。从患者的病历中收集CNS症状的发生率。超高效液相色谱法测定稳态时普瑞巴林的给药前血浆浓度。结果：稳态时普瑞巴林的血浆谷浓度具有很大的变异性，四分位数范围为0.43-1.2 mg/L/mg/kg，与肾小球滤过率（eGFR）呈负相关。在多元回归分析中，除eGFR（β=− 0.60）外，还确定了C反应蛋白（标准化偏回归系数，β= 0.31）和阿片类镇痛剂联合治疗（β= 0.24）。中枢神经系统症状的发生率显着增加与阿片类镇痛剂cotreatment和更高的格拉斯哥预后评分，但不与血浆普瑞巴林浓度的绝对值，eGFR，或其他临床实验室data.Conclusions：在癌症患者中，稳态谷血浆普瑞巴林浓度改变与肾功能，全身炎症，阿片类镇痛剂cotreatment。然而，在接受普瑞巴林治疗的癌症患者中观察到的CNS症状的发生率较高，与恶病质和阿片类镇痛药联合治疗的相关性大于普瑞巴林浓度改变。
Background:Patients with cancer 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 cotreatment.Methods:Sixty-eight patients with cancer receiving twice-daily pregabalin were enrolled. Plasma concentrations of pregabalin, clinical laboratory data, opioid analgesic cotreatment, and the Glasgow Prognostic Score, 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 predose plasma concentrations of pregabalin at steady state were 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 were negatively correlated with an estimated glomerular filtration rate (eGFR). C-reactive protein (standardized partial regression coefficient, β= 0.31) and opioid analgesic cotreatment (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 cotreatment and a higher Glasgow Prognostic Score but not with the absolute value of plasma pregabalin concentrations, eGFR, or other clinical laboratory data.Conclusions:In patients with cancer, steady-state trough plasma pregabalin concentrations were altered with renal function, systemic inflammation, and opioid analgesic cotreatment. However, a higher incidence of CNS symptoms observed in patients with cancer on pregabalin was more related to cachexia and opioid analgesic cotreatment than to altered pregabalin concentrations.