Aicua-Rapun Irene, André Pascal, Rossetti Andrea O, Decosterd Laurent A, Buclin Thierry, Novy Jan
Department of Clinical Neurosciences, Neurology Service, University Hospital (CHUV) and Faculty of Biology and Medicine of Lausanne, Switzerland.
Service of Clinical Pharmacology, University Hospital (CHUV) and Faculty of Biology and Medicine, Lausanne, Switzerland.
Epilepsy Res. 2019 Jan;149:88-91. doi: 10.1016/j.eplepsyres.2018.12.001. Epub 2018 Dec 3.
Brivaracetam is available in intravenous formulation, and its favourable pharmacokinetic profile makes it a promising agent in the treatment of status epilepticus (SE). Its availability as an intravenous formulation and its favourable pharmacokinetic profile make it a promising agent in the treatment of status epilepticus. Our aim was to assess the correlation between BRV exposure and clinical response. We retrospectively studied all consecutive SE patients treated with BRV in our centre from September 2016 to March 2018. Correlations between loading doses, plasma concentrations, extrapolated exposures (approach based on a population pharmacokinetics model) and the clinical response (defined as BRV being able to resolve SE without the need of further treatment), were analysed. Among 14 patients, 7 (50%) responded to BRV. Responders received significantly greater median loading dosage per body weight (3.3 mg/kg) compared to non-responders (1.5 mg/kg) (p = 0.02); no responders had loading doses below 1.9 mg/kg. There was a significant correlation of the clinical response with calculated exposure parameters, whereas measured BRV concentrations did not. BRV doses higher than 1.9 mg/kg are associated with greater probabilities of response in SE; consequently, a minimum dose of 2 mg/kg seems advisable in treatment of SE. It is unclear whether increasing further BRV loading doses would provide any additional benefit. BRV concentrations performed outside the frame of a standardised protocol merely ascertain BRV administration. This study is however limited by its small sample size.
布立伏胺有静脉制剂,其良好的药代动力学特征使其成为治疗癫痫持续状态(SE)的一种有前景的药物。其静脉制剂的可用性及其良好的药代动力学特征使其成为治疗癫痫持续状态的一种有前景的药物。我们的目的是评估布立伏胺暴露量与临床反应之间的相关性。我们回顾性研究了2016年9月至2018年3月在我们中心接受布立伏胺治疗的所有连续性SE患者。分析了负荷剂量、血浆浓度、外推暴露量(基于群体药代动力学模型的方法)与临床反应(定义为布立伏胺能够在无需进一步治疗的情况下解决SE)之间的相关性。在14例患者中,7例(50%)对布立伏胺有反应。与无反应者(1.5mg/kg)相比,有反应者每体重接受的中位负荷剂量显著更高(3.3mg/kg)(p = 0.02);无反应者的负荷剂量均未低于1.9mg/kg。临床反应与计算出的暴露参数有显著相关性,而实测的布立伏胺浓度则无此相关性。高于1.9mg/kg的布立伏胺剂量与SE中更高的反应概率相关;因此,在治疗SE时,建议最低剂量为2mg/kg。尚不清楚进一步增加布立伏胺负荷剂量是否会带来额外益处。在标准化方案框架之外进行的布立伏胺浓度检测仅能确定布立伏胺的给药情况。然而,本研究受样本量小的限制。