Discovery of Lacosamide Affinity Bait Agents That Exhibit Potent Voltage-Gated Sodium Channel Blocking Properties

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新疆维吾尔族、汉族癫痫患儿拉考沙胺血药浓度、临床疗效和安全性的差异性研究

目的 探讨新疆维吾尔族、汉族癫痫患儿拉考沙胺(lacosamide，LCM)血药浓度与临床疗效的相关性和差异性。方法 采用超高效液相色谱法测定100例维吾尔族癫痫患儿和194例汉族癫痫患儿的血药浓度，观察其疗效和不良反应，运用Logistic回归和受试者操作特征曲线分析患儿血药浓度和疗效的相关性。结果 维吾尔族患儿的LCM癫痫治疗有效率显著低于汉族患儿(65.00%和78.68%，P<0.05)。维吾尔族患儿的LCM血药浓度显著高于汉族患儿[(7.13±2.88)μg·mL^–1和(6.27±2.53)μg·mL^–1，P<0.05]。维吾尔族、汉族有效组患儿接受LCM单一治疗的比例显著高于无效组，接受LCM合并细胞色素P450酶诱导剂治疗的比例显著低于无效组(P<0.05)。维吾尔族、汉族癫痫患儿的不良反应发生率分别为29.00%和36.60%，发生不良反应的维吾尔族患儿的LCM血药浓度显著高于未发生不良反应组患儿[(8.20±3.60)μg·mL^–1和(6.70±2.43)μg·mL^–1，P<0.05]。结论 临床使用LCM治疗不同民族癫痫患儿的过程中，有必要监测LCM稳态谷浓度，以提高疗效和降低不良反应发生率。     

Lacosamide as treatment of epileptic seizures – cost utility results for Sweden

Bolin K, Berggren F, Forsgren L. Lacosamide as treatment of epileptic seizures – cost utility results for Sweden.
Acta Neurol Scand: 2010: 121: 406–412.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – To calculate cost per additional quality‐adjusted life‐year (QALY) for lacosamide as adjunctive treatment for patients with uncontrolled partial‐onset seizures as compared to no adjunctive treatment. Materials and methods – A decision‐tree simulation model was constructed to calculate the number of seizures and health‐care utilization for treated and untreated with lacosamide, respectively. Prices from 2007 were used for all costs. Results – All results were calculated for a 24‐, 18‐, 12‐ and 6‐months follow‐up. The cost per additional QALY was estimated to € 27,641 (24 months). Using a willingness‐to‐pay threshold for a QALY of € 50,000 the net marginal value of using lacosamide was estimated to about € 850,000 per 1000 patients. Conclusions – The estimated cost per QALY gained falls within the range of reported estimates of the willingness‐to‐pay for an additional QALY. The results imply that lacosamide is cost‐effective in the treatment of uncontrolled partial‐onset seizures (1 € ≈ 9.6 SEK).     

Third-generation antiepileptic drugs: mechanisms of action,pharmacokinetics and interactions

This review briefly summarizes the information on the molecular mechanisms of action, pharmacokinetic profiles and drug interactions of novel (third-generation) antiepileptic drugs, including brivaracetam, carabersat, carisbamate, DP-valproic acid, eslicarbazepine, fluorofelbamate, fosphenytoin, ganaxolone, lacosamide, losigamone, pregabalin, remacemide, retigabine, rufinamide, safinamide, seletracetam, soretolide, stiripentol, talampanel, and valrocemide. These novel antiepileptic drugs undergo intensive clinical investigations to assess their efficacy and usefulness in the treatment of patients with refractory epilepsy.     

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single‐centre study

Aim. Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centre's experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epilepsy. Methods. We retrospectively reviewed the medical records of 22 patients who received lacosamide from November 2009 to April 2014 at the CHU Ste‐Justine, University of Montreal. Treatment responders were defined as children with a ≥50% reduction in seizure frequency compared to baseline, and this was determined three months after the initiation of treatment and at the last follow‐up visit. Results. We included 14 boys and eight girls with a mean age of 12.9 years (SD: 5.2; range: 5.2–20.7 years) at the initiation of treatment. The average length of follow‐up was 11.9 months. Patients had previously received an average of 7.5 antiepileptic drugs. The mean number of concomitant antiepileptic drugs was 2.3. The mean initial and maintenance doses were 2.9 and 8.4 mg/kg/d, respectively. Thirteen (59%) and ten (45%) patients were responders after three months of treatment and at the last follow‐up visit, respectively. One became seizure‐free. Adverse effects were reported in 11 patients and none were severe. Responders and non‐responders were identical with respect to all studied parameters except gender, with the proportion of responders being greater in girls than in boys (75% vs 29%; p=0.035). Conclusion. Our study adds evidence that lacosamide appears to be a safe and effective adjunctive therapy for children with refractory focal epilepsy.     

The adverse-effect profile of lacosamide

ABSTRACT

Introduction: Lacosamide has been used in epilepsy patients in the United States, Europe and Asia since it was approved by the FDA in 2008. Many patients have benefited from this drug as a new generation of sodium channel blocker. With the worldwide use of this drug, its adverse effects have gradually emerged, especially some rare adverse events.

Areas covered: The present review aims to summarize the adverse effects of lacosamide reported in the literature in recent years to promote the safe clinical application of the drug.

Expert opinion: In more than 10 years of experience in drug usage, adverse reactions of lacosamide have also been gradually discovered. The review showed that lacosamide is safe and effective in antiepileptic treatment, and its common side effects are dizziness, headache, drowsiness, diplopia, and cardiovascular abnormalities. Skin rashes, hematotoxicity and heart damage, psychological symptoms and suicide risk have also been reported and emphasized.     

新疆癫痫患儿拉考沙胺血药浓度的影响因素探讨

目的：探讨年龄、性别、体质指数（body mass index,BMI）、族别和合并用药对新疆地区癫痫患儿拉考沙胺（lacosamide,LCM）稳态血药浓度的影响。方法：收集2019-2021年就诊于某院并规律服用LCM的0~14岁癫痫患儿的血清样本103例,用超高效液相色谱法进行血药浓度测定,并分析患儿年龄、性别、BMI、族别、给药剂量及合并用药等因素对其血药浓度的影响。结果：LCM的浓度剂量比（concentration-dose ratio,CDR）结果在男女性别之间的差异无统计学意义（t=-0.332;P=0.741）。学龄期年龄组患儿的CDR结果显著高于婴幼儿期和学龄前期组患儿（t=2.225,P=0.030;t=2.830,P=0.006）。BMI<18.5组患儿的CDR结果显著低于18.5≤BMI<24.0和BMI≥24.0组患儿（t=-2.876,P=0.006;t=-3.761,P=0.004）。维吾尔族癫痫患儿的CDR结果显著高于汉族癫痫患儿（t=-2.588,P=0.011）。结论：患儿临床应用LCM进行抗癫痫治疗,有必要对其进行血药浓度监测,以期为其个体化给药方案的建立提供理论依据。     

Tonic status epilepticus in a centenarian woman

Generalized tonic status epilepticus (TSE) is a rare epileptic condition. It occurs usually in the context of symptomatic generalized epilepsy, in particular, in subjects with a diagnosis of Lennox‐Gastaut syndrome, atypical forms of idiopathic (genetic) generalized epilepsy, or as a paradoxical effect during treatment with diverse antiepileptic drugs. Herein, we describe the case of an elderly woman on chronic treatment with psychotropic drugs who developed an episode of generalized TSE. Motor manifestations were subtle and difficult to recognize as seizures, and a detailed video‐EEG importantly contributed to accurate and prompt diagnosis. TSE was initially refractory to conventional anti‐seizure drug therapy including levetiracetam and valproate but was finally controlled with lacosamide. Our case indicates a potential therapeutic effect of lacosamide on TSE in the elderly after treatment failure with first‐line anti‐seizure drugs. [Published with video sequence on www.epilepticdisorders.com ]