The aim of this study was to investigate the influence of concomitant antiepileptic drugs (AEDs) on brivaracetam (BRV) trough serum concentrations. A total number of 368 routinely collected blood samples from 148 inpatients from Mara Hospital (Bethel Epilepsy Center) and von Bodelschwingh Foundation Bethel were retrospectively evaluated. Generalized estimation equations (GEEs) were used for statistical analysis. GEE analyses showed that BRV trough serum concentrations were significantly lower in patients with strong enzyme‐inducing AEDs (carbamazepine, phenytoin, and/or phenobarbital/primidone, −49%), but were not affected by concomitant intake of oxcarbazepine or eslicarbazepine. Age and gender did not have a significant effect. An alternative GEE model analyzing the BRV level‐to‐dose ratios yielded comparable results. Our results from routine therapeutic drug monitoring data indicate that the effect of enzyme‐inducing AEDs on BRV serum concentrations is stronger than the 20%‐30% reduction in BRV exposure previously reported in pharmacokinetics studies. Further research is necessary to evaluate these differences and to elucidate possible clinical consequences.

中文翻译：

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剂量和抗癫痫联合用药对癫痫患者布瓦西坦血药浓度的影响

本研究的目的是调查伴随抗癫痫药 (AED) 对布立西坦 (BRV) 谷血清浓度的影响。回顾性评估了来自马拉医院（伯特利癫痫中心）和冯博德尔施温基金会伯特利的148名住院患者的368份常规血液样本。广义估计方程 (GEE) 用于统计分析。GEE 分析显示，在使用强酶诱导 AED（卡马西平、苯妥英和/或苯巴比妥/扑米酮，-49%）的患者中，BRV 谷血清浓度显着降低，但不受同时服用奥卡西平或艾司利卡西平的影响。年龄和性别没有显着影响。另一种分析 BRV 水平剂量比的 GEE 模型产生了可比较的结果。我们来自常规治疗药物监测数据的结果表明，酶诱导型 AED 对 BRV 血清浓度的影响强于之前药代动力学研究中报告的 BRV 暴露减少 20%-30%。需要进一步研究来评估这些差异并阐明可能的临床后果。