Steinhoff Bernhard J, Georgiou Dimitra, Dietmann Daniel, Intravooth Tassanai
Kork Epilepsy Center, Kehl-Kork, 77694 Kehl, Germany.
Medical Faculty, University of Freiburg, 79104 Freiburg im Breisgau, Germany.
J Clin Med. 2024 May 8;13(10):2757. doi: 10.3390/jcm13102757.
Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) with ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies suggest high efficacy with unusually high seizure-free rates. The authors sought to investigate the plasma levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. Blood samples were collected from adult PWEs who were treated with adjunct cenobamate under steady-state conditions. Daily doses, concomitant medications, efficacy, and tolerability were assessed. The plasma cenobamate levels of seizure-free versus non-responding PWEs and between PWEs with and those without clinical adverse events were compared. Samples from 101 PWEs were included. Thirty-six PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. A linear correlation was found between the daily doses (range: 100 mg-400 mg) and the plasma levels (3.8 mg/L-54.6 mg/L). Neither the daily doses nor the plasma levels differed significantly between the investigated subgroups. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. To evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful. A general therapeutic range cannot be defined.
西诺巴胺已获欧洲药品管理局批准，用于治疗尽管使用至少两种已确立的抗癫痫药物进行了适当治疗，但仍有持续性局灶性发作的成年癫痫患者（PWEs）。关键试验和上市后真实世界观察性研究表明，其疗效显著，无癫痫发作率异常高。作者试图研究在稳态条件下，无癫痫发作的PWEs与无反应的PWEs之间，以及经历不良事件的PWEs与未经历不良事件的PWEs之间的西诺巴胺血浆水平。从在稳态条件下接受西诺巴胺辅助治疗的成年PWEs中采集血样。评估每日剂量、伴随用药、疗效和耐受性。比较了无癫痫发作的PWEs与无反应的PWEs之间，以及有临床不良事件的PWEs与无临床不良事件的PWEs之间的血浆西诺巴胺水平。纳入了101例PWEs的样本。36例PWEs无癫痫发作，65例无反应。31例PWEs出现不良事件，而其余70例未报告耐受性问题。发现每日剂量（范围：100mg - 400mg）与血浆水平（3.8mg/L - 54.6mg/L）之间存在线性相关性。研究的亚组之间每日剂量和血浆水平均无显著差异。该结果的主要原因是个体治疗范围差异很大：在一些PWEs中，低剂量和血浆水平时也观察到了无癫痫发作和不良反应。相反，也有一些PWEs的例子，他们在高剂量或血浆水平时无反应或未报告耐受性问题。为了评估个体治疗范围，并更好地了解在使用伴随用药的情况下其他药物的影响，西诺巴胺的治疗药物监测可能会有所帮助。无法定义一个通用的治疗范围。
