Efficacy and Serum Concentration of Lacosamide in Children with Epilepsy
ZHAO Ting1a,1b, SUN Yan2, ZHANG Hui-lan1a,1b, FENG Jie1a,1b, YU Jing2, WANG Ting-ting1a,1b, SUN Li1a,1b, LI Hong-jian1a,1b, YU Lu-hai1a,1b*
1a. Department of Pharmacy; 1b. Institute of Clinical Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000; 2. Department of Neurology, Children's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, China
Abstract：OBJECTIVE To study the efficacy, serum concentration and safety of lacosamide(LCM) in children with epilepsy, so as to provide reference for rational clinical drug use. METHODS The steady-state serum trough concentration of 148 children with epilepsy who took LCM orally was determined by Ultra high performance liquid chromatography to observe its clinical efficacy and adverse reactions. Logistic regression and subject operation characteristic curve were used to analyze the correlation between serum concentration and clinical efficacy. RESULTS The effective rate of LCM was 69%. The proportion of children with general and mixed seizures was significantly higher in the ineffective group than in the effective group (P<0.05). The frequency of abnormal electroencephalogram in the ineffective group was significantly higher than that in the effective group (P<0.05). The serum concentration of LCM and ratio of concentration-to-dose(CDR) in the ineffective group were significantly higher than those in the effective group (P<0.01). In addition, the proportion of children treated with LCM and inducers was significantly higher in the ineffective group than in the effective group (48% vs 25%, P<0.01). There was a good correlation between the clinical efficacy of LCM and CDR results (P<0.01). When the serum concentration of LCM was ≥3.50 μg·mL-1, the clinical efficacy could be better guaranteed. Forty-nine children (33%) experienced at least one adverse event, with dizziness, drowsiness, fatigue, and nausea being the most common adverse events. CONCLUSION In order to improve the clinical efficacy and reduce the incidence of adverse reactions, it is necessary to monitor the blood concentration of LCM in epileptic children.
赵婷, 孙岩, 张惠兰, 冯杰, 于静, 王婷婷, 孙力, 李红健, 于鲁海. 拉考沙胺在癫痫患儿中的临床疗效和血药浓度研究[J]. 中国药学杂志, 2022, 57(5): 403-407.
ZHAO Ting, SUN Yan, ZHANG Hui-lan, FENG Jie, YU Jing, WANG Ting-ting, SUN Li, LI Hong-jian, YU Lu-hai. Efficacy and Serum Concentration of Lacosamide in Children with Epilepsy. Chinese Pharmaceutical Journal, 2022, 57(5): 403-407.
PAUL Y. Various epileptic seizure detection techniques using biomedical signals: a review [J]. Brain Inform, 2018,5(2):6.
[2]
SHEN X M, WANG W P. Pediatrics (儿科学) [M]. Vol 7. Beijing: People's Health Publishing House, 2008: 390-391.
[3]
SANG T, XIANG T, ZHU SN, et al. Treatment-related costs of childhood epilepsy in mainland China: a preliminary study in a tertiary pediatric epilepsy center [J]. J Child Neurol, 2019, 34(2):68-73.
[4]
CHANG R S, LUI H K K, LUI H T C, et al. Efficacy upon 12-weeks after achievement of maximal dose and tolerability of lacosamide as an adjunctive therapy in epilepsy: Real world clinical experience[J]. J Neurol Sci, 2020, 15(409): 116601.
[5]
BITON V, GIL-NAGEL A, ISOJARVI J, et al. Safety and tolerability of lacosamide as adjunctive therapy for adults with partial-onset seizures: analysis of data pooled from three randomized, double-blind, placebo-controlled clinical trials[J]. Epilepsy Behav, 2015, 52(11): 119-127.
[6]
CONTIN M, ALBAN F, RIVA R, et al. Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs [J]. Ther Drug Monit, 2013, 35(6): 849-852.
[7]
MARKOULA S, TEOTONIO R, RATNARAJ N, et al. Lacosamide serum concentrations in adult patients with epilepsy: the influence of gender, age, dose, and concomitant antiepileptic drugs [J]. Ther Drug Monit, 2014, 36(4): 494-498.
[8]
SVENDSEN T, BRODTKORB E, BAFTIU A, et al. Therapeutic drug monitoring of lacosamide in Norway: focus on pharmacokinetic variability, efficacy and tolerability [J]. Neurochem Res, 2017, 42(7): 2077-2083.
[9]
JULIA W, RIK S, ARMEL S. Modeling and simulation for the evaluation of dose adaptation rules of intravenous lacosamide in children[J]. Epilepsy Res, 2019, 149:13-16.
[10]
PHILIP N. Pediatric antiepileptic drug therakpeutic drug monitoring[J]. J Pediatr Pharm(儿科药学杂志), 2016, 22(3): 12-17.
[11]
PATSALOS P N, BERRY D J, BOURGEOIS B F D, et al. Antiepileptic drugs-Best practice guidelines for therapeutic drug monitoring: A position paper by the Subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies[J]. Epilepsia, 2008, 49(9): 1239-1276.
[12]
SHAH A, MICHELHAUGH S, MLTTAL S. Therapeutic use of lacosamide does not alter its distribution between serum and cerebrospinal fluid[J]. Epilepsy Curr, 2015, 56(11):1732-1737.
[13]
CHRISTIAN B, CHRISTIAN G B, RENATE H. Assessment of the correlations of lacosamide concentrations in saliva and serum in patients with epilepsy[J]. Epilepsia, 2018, 59(4):e34-e39.
[14]
FARKAS V, STEINBORN B, FLAMINI J R, et al. Efficacy and tolerability of adjunctive lacosamide in pediatric patients with focal seizures[J]. Neurology, 2019, 93(12):e1212-e1226.
[15]
HEYMAN E, LAHAT E, LEVIN N, et al. Preliminary efficacy and safety of lacosamide in children with refractory epilepsy[J]. Eur J Paediatr Neurol,2012,16(1):15-19.
[16]
SANMARTOI-VILAPLANA F, DIAZ-GOMEZ A. The effectiveness and safety of lacosamide inchildren with epilepsy in a clinical practice setting[J]. Epilepsy Behav,2018,79(2):130-137.
[17]
MAY T W, HELMER R, BIEN C G, et al. Influence of dose and antiepileptic comedication on lacosamide serum concentrations in patients with epilepsy of different ages[J]. Ther Drug Monit, 2018, 40(5):620-627.
[18]
YAMAMOTO Y, TERADA K, ARAKI Y, et al. Therapeutic monitoring of lacosamide in Japanese patients with epilepsy: clinical response, tolerability, and optimal therapeutic range[J]. Ther Drug Monit, 2020, 42(5):754-759.
2022, Vol. 57 
