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Third generation antiepileptic drugs: mechanism of action, pharmacokinetics, interaction and use in childhood

https://doi.org/10.17749/2077-8333/epi.par.con.2023.149

Abstract

The review considers pharmacological characteristics of new antiepileptic drugs (AEDs) of the third generation such as eslicarbazepine, lacosamide, retigabine, perampanel, everolimus, brivaracetam, zonisamide. The data on the mechanisms of action, pharmacokinetics, drug interactions, indications for use and side effects are presented. The drugs are recognized as superior in safety and efficacy to previously known AEDs of the first and second generations. The majority of new AEDs is used to control focal seizures, as well as in specific epileptic syndromes (Lennox–Gastaut syndrome, Dravet syndrome), and tuberous sclerosis. The drugs differ in the mechanism of action, pharmacokinetic properties, effectiveness and profile of side effects, which account for an opportunity to apply a personalized approach to patient treatment. Properly selected therapy allows to achieve good control over epileptic seizures as well as lower a risk of disease-related complications. While prescribing AEDs, it is necessary to take into account their pharmacokinetic and pharmacodynamic features.

About the Authors

Z. G. Tadtaeva
Saint Petersburg Pediatric Medical University
Russian Federation

Zara G. Tadtaeva – Dr. Med. Sc., Professor, Chair of Pharmacology with the Course of Clinical Pharmacology and Pharmacoeconomics

2 Litovskaya Str., Saint Petersburg 194100



A. N. Galustyan
Saint Petersburg Pediatric Medical University
Russian Federation

Anna N. Galustyan – MD, PhD, Associate Professor, Chief of Chair of Pharmacology with the Course of Clinical Pharmacology and Pharmacoeconomics

2 Litovskaya Str., Saint Petersburg 194100



O. A. Gromova
Federal Research Center “Computer Science and Control”, RAS
Russian Federation

Olga A. Gromova – Dr. Med. Sc., Professor, Research Supervisor, Institute of Pharmacoinformatics

WoS ResearcherID: J-4946- 2017; Scopus Author ID: 7003589812

4 Vavilov Str., Moscow 211933



I. S. Sardaryan
Saint Petersburg Pediatric Medical University
Russian Federation

Ivan S. Sardaryan – MD, PhD, Associate Professor, Chair of Pharmacology with the Course of Clinical Pharmacology and Pharmacoeconomics, Saint Petersburg Pediatric Medical University

Scopus Author ID: 57200672112

2 Litovskaya Str., Saint Petersburg 194100



References

1. Karlov V.A. Epilepsy in children and adult men and women. A guide for doctors. 2nd ed. Moscow: Binom; 2019: 896 pp. (in Russ.).

2. Devinsky O., Vezzani A., O’Brien T.J., et al. Epilepsy. Nat Rev Dis Primers. 2018; 4: 18024. https://doi.org/10.1038/nrdp.2018.24.

3. Janmohamed M., Brodie M.J., Kwan P. Pharmacoresistance – epidemiology, mechanisms, and impact on epilepsy treatment. Neuropharmacology. 2020; 168: 107790. https://doi.org/10.1016/j.neuropharm.2019.107790.

4. Perucca E., Brodie M.J., Kwan P., Tomson T. 30 years of secondgeneration antiseizure medications: impact and future perspectives. Lancet Neurol. 2020; 19 (6): 544–56. https://doi.org/10.1016/S14744422(20)30035-1.

5. Nakken K.O., Brodtkorb E. Are new anti-epileptic drugs any better than their predecessors? Tidsskr Nor Laegeforen. 2020;140 (17). https://doi.org/10.4045/tidsskr.20.0657.

6. Trinka E., Ben-Menachem E., Kowacs P.A., et al. Efficacy and safety of eslicarbazepine acetate versus controlled-release carbamazepine monotherapy in newly diagnosed epilepsy: a phase III double-blind, randomized, parallel-group, multicenter study. Epilepsy. 2018; 59 (2): 479–91. https://doi.org/10.1111/epi.13993.

7. Sills G.J., Rogawski M.A. Mechanisms of action of currently used antiseizure drugs. Neuropharmacology. 2020; 168: 107966. https://doi.org/10.1016/j.neuropharm.2020.107966.

8. Curatolo P., Napolioni V., Moavero R. Autism spectrum disorders in tuberous sclerosis: pathogenetic pathways and implications for treatment. J Child Neurol. 2010; 25 (7): 873–80. https://doi.org/10.1177/0883073810361789.

9. State register of medicines. Available at: http://grls.rosminzdrav.ru (in Russ.) (accessed 25.02.2023).

10. Mukhin K.Yu., Pylaeva O.A. Use of perampanel in the treatment of epilepsy: a review of literature and a case report. Russian Journal of Child Neurology. 2016; 11 (2): 52–62 (in Russ.). https://doi.org/10.17650/2073-8803-2016-11-2-52-62.

11. Rektor I., Krauss G.L., Bar M., et al. Perampanel Study 207: long-term open-label evaluation in patients with epilepsy. Acta Neurol Scand. 2012; 126 (4): 263–9. https://doi.org/10.1111/ane.12001.

12. Patsalos P.N. The сlinical рharmacology рrofile of the new antiepileptic drug perampanel: а novel noncompetitive AMPA receptor аntagonist. Epilepsia. 2015; 56 (1): 12–27. https://doi.org/10.1111/epi.12865.

13. Dredge D.C. (Ed.) Handbook of pediatric epilepsy education. Springer; 2022: 447 pp.

14. Jóźwiak S., Vegiotti P., Moreira J., et al. Effects of adjunctive eslicarbazepine acetate on neurocognitive functioning in children with refractory focal-onset seizures. Epilepsy Behav. 2018; 81: 1–11. https://doi.org/10.1016/j.yebeh.2018.01.029.

15. Parada A., Soares-da-Silva P. The novel anticonvulsant BIA 2-093 inhibits transmitter release during opening of voltage-gated sodium channels: a comparison with carbamazepine and oxcarbazepine. Neurochem Int. 2002; 40 (5): 435–40. https://doi.org/10.1016/S01970186(01)00101-2.

16. Bonifácio M.J., Sheridan R.D., Parada A., et al. Interaction of the new anticonvulsant, BIA 2-093, with voltage-gate sodium channels: comparison with carbamazepine. Epilepsy. 2001; 42 (5): 600–8. https://doi.org/10.1046/j.1528-1157.2001.43600.x.

17. Galiana G.L., Gauthier A.C., Mattson R.H. Eslicarbazepine acetate: a new improve ment on a classic drug family for the treatment of partial-onset seizures. Drugs R D. 2017; 17 (3): 329–39. https://doi.org/10.1007/s40268-017-0197-5.

18. Mäkinen J., Rainesalo S., Peltola J. Transition from oxcarbazepine to eslicarbazepine acetate: a single center study. Brain Behav. 2017; 7 (3): e00634. https://doi.org/10.1002/brb3.634.

19. Ben-Menachem E., Gabay A.A., Hufnagel A., et al. Eslicarbazepine acetate as an adjunct therapy in adult patients with partial epilepsy. Epilepsy Res. 2010; 89 (2–3): 278–85. https://doi.org/10.1016/j.eplepsyres.2010.01.014.

20. Nunes T., Sicard E., Almeida L., et al. Pharmacokinetic interaction study between eslicarbazepin and topiramate in healthy volunteers. Curr Med Res Opinion. 2010; 26 (6): 1355–62. https://doi.org/10.1185/03007991003740861.

21. Singh R.P., Asconapé J.J. A review of eslicarbazepine acetate for the adjunctive treatment of partial-onset epilepsy. J Cent Nerv Syst Dis. 2011; 3: 179–87. https://doi.org/10.4137/JCNSD.S4888.

22. Luzhczky J.J. Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. Pharmacol Rep. 2009; 61 (2): 197–216. https://doi.org/10.1016/s1734-1140(09)70024-6.

23. Ortiz de la Rosa J.S., Ladino L.D., Rodríguez L.D., et al. Efficacy of lacosamide in children and adolescents with drug-resistant epilepsy and refractory epileptic status: a systematic review. Seizure. 2018; 56: 34–40. https://doi.org/10.1016/j.seizure.2018.01.014.

24. Rogawski M.A., Tofighi A., White H.S., et al. Current understanding of the mechanism of action of the antiepileptic drug lacosamide. Epilepsy Res. 2015; 110: 189–205. https://doi.org/10.1016/j.eplepsyres.2014.11.021.

25. Rosenfeld V., Fountain N.B., Kaubrys G., et al. Safety and efficacy of adjunctive lacosamide among patients with partialonset seizures in a long-term open-label extension trial of up to 8 years. Epilepsy Behav. 2014; 41: 164–70. https://doi.org/10.1016/j.yebeh.2014.09.074.

26. Harris J.A., Murphy J.A. Lacosamide and еpilepsy. CNS Neurosci Ther. 2011; 17 (6): 678–82. https://doi.org/10.1111/j.17555949.2010.00198.x.

27. Martyn-St James M., Glanville J., McCool R., et al. The efficacy and safety of retigabine and other adjunctive treatments for refractory partial epilepsy: a systematic review and indirect comparison. Seizure. 2012; 21 (9): 665–78. https://doi.org/10.1016/j.seizure.2012.07.011.

28. Abbou-Khalil B.W. Update on antiepileptic drugs 2019. Continuum (Minneap Minn). 2019; 25 (2): 508–36. https://doi.org/10.1212/CON.0000000000000715.

29. Walleigh D.J., Legido A., Valencia I. Ring chromosome 20: a pediatric potassium channelopathy responsive to treatment with ezogabine. Pediatr Neurol. 2013; 49 (5): 368–9. http://doi.org/10.1016/j.pediatrneurol.2013.06.005.

30. Bialer M., Johannessen S.I., Kupferberg H.J., et al. Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII). Epilepsy Res. 2004; 61 (1–3): 1–48. http://doi.org/10.1016/j.eplepsyres.2004.07.010.

31. Koltzenburg M., McMahon S.B., Tracey I., Turk D.C. (Eds.) Wall and Melzak's textbook of pain. 6th ed. Philadelphia, PA: Elsevier/Saunders; 2013: 1153 pp.

32. Grigoryeva A.V., Dorofeeva M.Yu., Perminov V.S., Belousova E.D. A retrospective analysis of the efficacy and tolerability of treatment with everolimus in treatment-refractory epilepsy associated with tuberous sclerosis. Almanac of Clinical Medicine. 2020; 48 (1): 1–6 (in Russ.). http://doi.org/10.18786/2072-0505-2020-48-003.

33. French J.A., Lawson J.A., Yapichi Z., et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016; 388 (10056): 2153–63. http://doi.org/10.1016/S0140-6736(16)31419-2.

34. Svarrer E.M.M., Fischer C.M., Frederiksen M.G., et al. Everolimus as adjunctive treatment in tuberous sclerosis complex-associated epilepsy in children. Dan Med J. 2019; 66 (12): A5582.

35. Lechuga L., Franz D.N. Everolimus as adjunctive therapy for tuberous sclerosis complex-associated partial-onset seizures. Expert Rev Neurother. 2019; 19 (10): 913–25. http://doi.org/10.1080/14737175.2019.1635457.

36. Kornilov D.O., Tryapitsyn M.A., Grebnev D.Yu. mTOR: signaling, regulation, effect on metabolism, role in the regulation of life expectancy and tumor growth. Proceedings of the Komi Science Center of the Ural Division of the Russian Academy of Sciences. Series "Experimental Biology and Ecology". 2021; 5: 104–14 (in Russ.). http://doi.org/10.19110/1994-5655-2021-5-104-115.

37. MacKeigan J.P., Krueger D.A. Differentiating the mTOR inhibitors everolimus and sirolimus in the treatment of tuberous sclerosis complex. Neuro Oncol. 2015; 17 (12): 1550–9. http://doi.org/10.1093/neuonc/nov152.

38. Li M., Zhou Y., Chen C., et al. Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis. Orphanet J Rare Dis. 2019; 14 (1): 39. http://doi.org/10.1186/s13023-019-1012-x.

39. Ryther R.C., Wong M. Mammalian target of rapamycin (mTOR) inhibition: potential for antiseizure, antiepileptogenic, and epileptostatic therapy. Curr Neurol Neurosci Rep. 2012; 12 (4): 410–8. http://doi.org/10.1007/s11910-012-0276-5.

40. Kirchner G.I., Meier-Wiedenbach I., Manns M.P. Clinical pharmacokinetics of everolimus. Clin Pharmacokinet. 2004; 43 (2): 83–95. http://doi.org/10.2165/00003088-200443020-00002.

41. Franz D.N., Lawson J.A., Yapici Z., et al. Everolimus dosing recommendations for tuberous sclerosis complex-associated refractory seizures. Epilepsia. 2018; 59 (6): 1188–97. http://doi.org/10.1111/epi.14085.

42. Arzimanoglou A., D‘Cruz O., Nodli D., et al. A review of the new antiepileptic drugs for focal-onset seizures in pediatrics: role of extrapolation. Pediatr Drugs. 2018; 20 (3): 249–64. http://doi.org/10.1007/s40272-018-0286-0.

43. Liu E., Dilley D., McDonough B., et al. Safety and tolerability of adjunctive brivaracetam in pediatric patients < 16 years with epilepsy: an open-label trial. Pediatr Drugs. 2019; 21 (4): 291–301. http://doi.org/10.1007/s40272-019-00332-y.

44. Klitgaard H., Matagne A., Nicolas J.M., et al. Brivaracetam: Rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia. 2016; 57 (4): 538–48. http://doi.org/10.1111/epi.13340.

45. Strzelczyk A., Klein K.M., Willems L.M., et al. Brivaracetam in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus. Expert Rev Clin Pharmacol. 2016; 9 (5): 637–45. http://doi.org/10.1586/17512433.2016.1156529.

46. Sargentini-Maier M.L., Rolan P., Connell J., et al. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males. Br J Clin Pharmacol. 2007; 63 (6): 680–8. http://doi.org/10.1111/j.13652125.2006.02829.x.

47. Nicholas J.M., Hannestad J., Holden D., et al. Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia. 2016; 57 (2): 201–9. http://doi.org/10.1111/epi.13267.

48. Rolan P., Sargentini-Maier M.L., Pigeolet E., Stockis A. The pharmacokinetics, CNS pharmacodynamics and adverse event profile ofbrivaracetam after multiple increasing oral doses in healthy men. Br J Clin Pharmacol. 2008; 66 (1): 71–5. http://doi.org/10.1111/j.13652125.2008.03158.x.

49. von Rosenstiel P. Brivaracetam (UCB 34714). Neurotherapeutics. 2007; 4 (1): 84–7. http://doi.org/10.1016/j.nurt.2006.11.004.

50. Kwan S.Y., Chuang Y.C., Huang C.W., et al. Zonisamide: review of recent clinical evidence for treatment of epilepsy. CNS Neurosci Ther. 2015; 21 (9): 683–91. http://doi.org/10.1111/cns.12418.

51. Cornes S.B., Griffn Jr. E.A., Lowenstein D.H. Pharmacology of abnormal electrical neurotransmission in the central nervous system. In: Golan D.E., Armstrong E.J., Armstrong A.W. Principles of pharmacology: the pathophysiologic basis of drug therapy. 4th ed. Philadelphia: Wolters Kluwer; 2017: 249–64.

52. Holder J.L. Jr., Wilfong A.A. Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2011; 12 (16): 2573–81. http://doi.org/10.1517/14656566.2011.622268.

53. Hoy S.M. Zonisamide: a review of its use in the management of adults with partial seizures. Drugs. 2013; 73 (12): 1321–38. http://doi.org/10.1007/s40265-013-0093-4.

54. Misty D.M., Metcalf C.S., Wilcox K.S. Pharmacotherapy of the epilepsies. In: Brunton L.L., Hilal-Dandan R., Knollmann B.C. (Eds.) Goodman and Gilman’s: the pharmacological basis of therapeutic. 13th ed. McGraw-Hill; 2018.

55. Brody M.J., Ben-Menachem E., Schmitt I., Georgie L. Zonisamide: its pharmacology, efficacy and safety in clinical trials. Acta Neurol Scand. 2012; 126 (Appendix 194): 19–28.


Review

For citations:


Tadtaeva Z.G., Galustyan A.N., Gromova O.A., Sardaryan I.S. Third generation antiepileptic drugs: mechanism of action, pharmacokinetics, interaction and use in childhood. Epilepsy and paroxysmal conditions. 2023;15(2):160-170. (In Russ.) https://doi.org/10.17749/2077-8333/epi.par.con.2023.149

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ISSN 2077-8333 (Print)
ISSN 2311-4088 (Online)