Research progress of perampanel in the treatment of childhood epilepsy_Journal of Epilepsy

Authors：

SUN Yuyao ¹ ,  YANG Xinwei ²

1. Xi’an Medical College, Xi’an 710000, China;
2. Department of Paediatrics, the First Affiliated Hospital of the Air Force Military Medical University, Xi’an 710000, China;

Corresponding author：

YANG Xinwei, Email: 693647291@qq.com

Keywords：

Epilepsy children; Perampanel; Antiseizure medications; Efficacy

DOI：

10.7507/2096-0247.202302007

Video：

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Perampanel (PER) is a third-generation novel anti-seizure drug, a postsynaptic neuronal (α-Amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid, AMPA) receptor antagonist, which effectively controls seizures by inhibiting glutamate-induced neurological hypertransmission. PER can not only be used for the addition of focal epilepsy 4 years old and above, but also monotherapy for children (≥ 4 years old) for the treatment of focal epilepsy patients, its efficacy and safety is relatively good, has been used clinically in many countries, the article overviewed the pharmacokinetics, mechanism, and the addition and monotherapy in different epilepsy types of childhood epilepsy and other aspects, in order to provide a reference for clinical medication, and provide individualized treatment for children with epilepsy.

Citation： SUN Yuyao, YANG Xinwei. Research progress of perampanel in the treatment of childhood epilepsy. Journal of Epilepsy, 2023, 9(3): 218-223. doi: 10.7507/2096-0247.202302007 Copy

1.	Soleman J, Knorr C, Datta AN, et al. Early vagal nerve stimulator implantation in children: personal experience and review of the literature. Child's Nervous System, 2018, 34(5): 893-900.
2.	孙丰森, 张世鹏, 许述, 等. 4种抗癫痫新药的研究和开发. 国际药学研究杂志, 2018, 45(11): 845-851.
3.	Omran A, Elimam D, Yin F. MicroRNAs: new insights into chronic childhood diseases. BioMed Research International, 2013, 18(29): 1-13.
4.	秦炯. 导言: 中国儿童癫痫诊治现状与专家共识. 医学与哲学(临床决策论坛版), 2010, 31(8): 5.
5.	David G. Vossler MFMW, PharmD BEGP. working toward a world without epilepsy. American Epilepsy Society, 2018, 18(2): 1-26.
6.	BRODIE MJ, BARRY SJE, BAMAGOUS GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology, 2012, 78(20): 1548-1554.
7.	何伟亮, 吴惠珍, 刘平, 等. 吡仑帕奈抗癫痫的药理作用和临床评价. 中国新药与临床杂志, 2022, 41(3): 138-142.
8.	查彩慧, 郭国庆. 突触后神经元AMPA受体循环的机制. 暨南大学学报(自然科学与医学版), 2018, 39(04): 277-286.
9.	Potschka H, Trinka E. Perampanel: does it have broad-spectrum potential? Epilepsia, 2019, 60: 22-36.
10.	Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Curr, 2011, 11(2): 56-63.
11.	Niu H, Wang J, Wang D, et al. The orally active noncompetitive ampar antagonist perampanel attenuates focal cerebral ischemia injury in rats. Cellular and Molecular Neurobiology, 2018, 38(2): 459-466.
12.	Leo A, Giovannini G, Russo E, et al. The role of AMPA receptors and their antagonists in status epilepticus. Epilepsia, 2018, 59(6): 1098-1108.
13.	吴晔, 操德智, 冯建华, 等. 儿童癫痫患者中吡仑帕奈使用的专家建议. 癫痫杂志, 2022, 8(2): 95-98.
14.	Fogarasi A, Flamini R, Milh M, et al. Open‐label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizures or generalized tonic‐clonic seizures. Epilepsia, 2020, 61(1): 125-137.
15.	De Liso P, Moavero R, Coppola G, et al. Current role of perampanel in pediatric epilepsy. Italian Journal of Pediatrics, 2017, 43(1): 1-6.
16.	Steinhoff BJ, Ben-Menachem E, Ryvlin P, et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia, 2013, 54(8): 1481-1489.
17.	Yamamoto Y, Shiratani Y, Asai S, et al. Pharmacokinetics, tolerability, and clinical effectiveness of perampanel in Japanese patients with epilepsy. Seizure, 2020, 83: 181-186.
18.	Yamamoto T, Lim SC, Ninomiya H, et al. Efficacy and safety of perampanel monotherapy in patients with focal‐onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: the open‐label study 342 (FREEDOM Study). Epilepsia Open, 2020, 5(2): 274-284.
19.	Kim JH, Kim DW, Lee SK, et al. First add‐on perampanel for focal‐onset seizures: an open‐label, prospective study. Acta Neurologica Scandinavica, 2019, 141(2): 132-140.
20.	Villanueva V, Montoya J, Castillo A, et al. Perampanel in routine clinical use in idiopathic generalized epilepsy: the 12-month GENERAL study. Epilepsia, 2018, 59(9): 1740-1752.
21.	Biró A, Stephani U, Tarallo T, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies: first experiences. Neuropediatrics, 2015, 46(02): 110-115.
22.	张宇昕, 翟琼香, 张静雯, 等. 应用吡仑帕奈对小儿难治性癫痫添加治疗的临床研究. 癫痫杂志, 2022, 8(3): 232-235.
23.	Hwanga S, Yun-Jin Leeb C, Sang Ook Namb C, et al. Real-life effectiveness and tolerability of perampanel in pediatric patients aged 4 years or older with epilepsy: a Korean national multicenter study. Journal of Clinical Neurolog, 2020, 16(1): 53-59.
24.	Lin K, Lin J, Chou M, et al. Efficacy and tolerability of perampanel in children and adolescents with pharmacoresistant epilepsy: the first real-world evaluation in asian pediatric neurology clinics. Epilepsy & Behavior, 2018, 85: 188-194.
25.	张捷, 吴晔, 谢涵, 等. 基于随访6个月疗效结局的加用吡仑帕奈治疗儿童药物难治性癫的单中心前瞻性队列研究. 中国循证儿科杂志, 2021, 16(4): 269-274.
26.	Dan Li SHXW. Efficacy and adverse reactions of perampanel in the treatment of epilepsy in children. Frontiers in Neurology, 2013, 12: 924057.
27.	Crespel A, Tang NPL, Macorig G, et al. Open-label, uncontrolled retrospective study of perampanel in adults with Lennox-Gastaut syndrome. Seizure, 2020, 75: 66-69.
28.	Gschwind M, Seeck M. Modern management of seizures and epilepsy. Swiss Medical Weekly, 2013（10.1155/2013/291826）.
29.	Gil-Nagel A, Burd S, Toledo M, et al. A retrospective, multicentre study of perampanel given as monotherapy in routine clinical care in people with epilepsy. Seizure, 2018, 54: 61-66.
30.	Toledano Delgado R, García Morales I, Parejo Carbonell B, et al. Effectiveness and safety of perampanel monotherapy for focal and generalized tonic‐clonic seizures: experience from a national multicenter registry. Epilepsia, 2020, 61(6): 1109-1119.
31.	Meador KJ, Yang H, Pina-Garza JE, et al. Cognitive effects of adjunctive perampanel for partial-onset seizures: a randomized trial. Epilepsia, 2016, 57(2): 243-251.
32.	Piña-Garza JE, Lagae L, Villanueva V, et al. Long-term effects of adjunctive perampanel on cognition in adolescents with partial seizures. Epilepsy & Behavior, 2018, 83: 50-58.
33.	Ettinger AB, LoPresti A, Yang H, et al. Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel. Epilepsia, 2015, 56(8): 1252-1263.
34.	Trinka E, Steinhoff BJ, Nikanorova M, et al. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurologica Scandinavica, 2016, 133(3): 160-172.
35.	Ikemoto S, Hamano S, Hirata Y, et al. Efficacy and serum concentrations of perampanel for treatment of drug-resistant epilepsy in children, adolescents, and young adults: comparison of patients younger and older than 12 years. Seizure, 2019, 73: 75-78.

1. Soleman J, Knorr C, Datta AN, et al. Early vagal nerve stimulator implantation in children: personal experience and review of the literature. Child's Nervous System, 2018, 34(5): 893-900.
2. 孙丰森, 张世鹏, 许述, 等. 4种抗癫痫新药的研究和开发. 国际药学研究杂志, 2018, 45(11): 845-851.
3. Omran A, Elimam D, Yin F. MicroRNAs: new insights into chronic childhood diseases. BioMed Research International, 2013, 18(29): 1-13.
4. 秦炯. 导言: 中国儿童癫痫诊治现状与专家共识. 医学与哲学(临床决策论坛版), 2010, 31(8): 5.
5. David G. Vossler MFMW, PharmD BEGP. working toward a world without epilepsy. American Epilepsy Society, 2018, 18(2): 1-26.
6. BRODIE MJ, BARRY SJE, BAMAGOUS GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology, 2012, 78(20): 1548-1554.
7. 何伟亮, 吴惠珍, 刘平, 等. 吡仑帕奈抗癫痫的药理作用和临床评价. 中国新药与临床杂志, 2022, 41(3): 138-142.
8. 查彩慧, 郭国庆. 突触后神经元AMPA受体循环的机制. 暨南大学学报(自然科学与医学版), 2018, 39(04): 277-286.
9. Potschka H, Trinka E. Perampanel: does it have broad-spectrum potential? Epilepsia, 2019, 60: 22-36.
10. Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Curr, 2011, 11(2): 56-63.
11. Niu H, Wang J, Wang D, et al. The orally active noncompetitive ampar antagonist perampanel attenuates focal cerebral ischemia injury in rats. Cellular and Molecular Neurobiology, 2018, 38(2): 459-466.
12. Leo A, Giovannini G, Russo E, et al. The role of AMPA receptors and their antagonists in status epilepticus. Epilepsia, 2018, 59(6): 1098-1108.
13. 吴晔, 操德智, 冯建华, 等. 儿童癫痫患者中吡仑帕奈使用的专家建议. 癫痫杂志, 2022, 8(2): 95-98.
14. Fogarasi A, Flamini R, Milh M, et al. Open‐label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizures or generalized tonic‐clonic seizures. Epilepsia, 2020, 61(1): 125-137.
15. De Liso P, Moavero R, Coppola G, et al. Current role of perampanel in pediatric epilepsy. Italian Journal of Pediatrics, 2017, 43(1): 1-6.
16. Steinhoff BJ, Ben-Menachem E, Ryvlin P, et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia, 2013, 54(8): 1481-1489.
17. Yamamoto Y, Shiratani Y, Asai S, et al. Pharmacokinetics, tolerability, and clinical effectiveness of perampanel in Japanese patients with epilepsy. Seizure, 2020, 83: 181-186.
18. Yamamoto T, Lim SC, Ninomiya H, et al. Efficacy and safety of perampanel monotherapy in patients with focal‐onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: the open‐label study 342 (FREEDOM Study). Epilepsia Open, 2020, 5(2): 274-284.
19. Kim JH, Kim DW, Lee SK, et al. First add‐on perampanel for focal‐onset seizures: an open‐label, prospective study. Acta Neurologica Scandinavica, 2019, 141(2): 132-140.
20. Villanueva V, Montoya J, Castillo A, et al. Perampanel in routine clinical use in idiopathic generalized epilepsy: the 12-month GENERAL study. Epilepsia, 2018, 59(9): 1740-1752.
21. Biró A, Stephani U, Tarallo T, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies: first experiences. Neuropediatrics, 2015, 46(02): 110-115.
22. 张宇昕, 翟琼香, 张静雯, 等. 应用吡仑帕奈对小儿难治性癫痫添加治疗的临床研究. 癫痫杂志, 2022, 8(3): 232-235.
23. Hwanga S, Yun-Jin Leeb C, Sang Ook Namb C, et al. Real-life effectiveness and tolerability of perampanel in pediatric patients aged 4 years or older with epilepsy: a Korean national multicenter study. Journal of Clinical Neurolog, 2020, 16(1): 53-59.
24. Lin K, Lin J, Chou M, et al. Efficacy and tolerability of perampanel in children and adolescents with pharmacoresistant epilepsy: the first real-world evaluation in asian pediatric neurology clinics. Epilepsy & Behavior, 2018, 85: 188-194.
25. 张捷, 吴晔, 谢涵, 等. 基于随访6个月疗效结局的加用吡仑帕奈治疗儿童药物难治性癫的单中心前瞻性队列研究. 中国循证儿科杂志, 2021, 16(4): 269-274.
26. Dan Li SHXW. Efficacy and adverse reactions of perampanel in the treatment of epilepsy in children. Frontiers in Neurology, 2013, 12: 924057.
27. Crespel A, Tang NPL, Macorig G, et al. Open-label, uncontrolled retrospective study of perampanel in adults with Lennox-Gastaut syndrome. Seizure, 2020, 75: 66-69.
28. Gschwind M, Seeck M. Modern management of seizures and epilepsy. Swiss Medical Weekly, 2013（10.1155/2013/291826）.
29. Gil-Nagel A, Burd S, Toledo M, et al. A retrospective, multicentre study of perampanel given as monotherapy in routine clinical care in people with epilepsy. Seizure, 2018, 54: 61-66.
30. Toledano Delgado R, García Morales I, Parejo Carbonell B, et al. Effectiveness and safety of perampanel monotherapy for focal and generalized tonic‐clonic seizures: experience from a national multicenter registry. Epilepsia, 2020, 61(6): 1109-1119.
31. Meador KJ, Yang H, Pina-Garza JE, et al. Cognitive effects of adjunctive perampanel for partial-onset seizures: a randomized trial. Epilepsia, 2016, 57(2): 243-251.
32. Piña-Garza JE, Lagae L, Villanueva V, et al. Long-term effects of adjunctive perampanel on cognition in adolescents with partial seizures. Epilepsy & Behavior, 2018, 83: 50-58.
33. Ettinger AB, LoPresti A, Yang H, et al. Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel. Epilepsia, 2015, 56(8): 1252-1263.
34. Trinka E, Steinhoff BJ, Nikanorova M, et al. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurologica Scandinavica, 2016, 133(3): 160-172.
35. Ikemoto S, Hamano S, Hirata Y, et al. Efficacy and serum concentrations of perampanel for treatment of drug-resistant epilepsy in children, adolescents, and young adults: comparison of patients younger and older than 12 years. Seizure, 2019, 73: 75-78.

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