Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures

Frank MC Besag,1–3 Philip N Patsalos4,51East London Foundation NHS Trust, 2Institute of Psychiatry, Psychology and Neuroscience, 3UCL School of Pharmacy, 4Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, NIHR University College London Hospitals Biomedical Resea...

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Autores principales:	Besag FM, Patsalos PN
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	perampanel new antiepileptic drug epilepsy primary generalized seizures pharmacokinetics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/d67b18ba8ba34c7fa16d616bc275362a
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spelling	oai:doaj.org-article:d67b18ba8ba34c7fa16d616bc275362a2021-12-02T01:27:26ZClinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures1178-2021https://doaj.org/article/d67b18ba8ba34c7fa16d616bc275362a2016-05-01T00:00:00Zhttps://www.dovepress.com/clinical-efficacy-of-perampanel-for-partial-onset-and-primary-generali-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Frank MC Besag,1–3 Philip N Patsalos4,51East London Foundation NHS Trust, 2Institute of Psychiatry, Psychology and Neuroscience, 3UCL School of Pharmacy, 4Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, NIHR University College London Hospitals Biomedical Research Centre, London, 5Epilepsy Society, Chalfont Centre for Epilepsy, Chalfont St Peter, UKBackground and purpose: Perampanel, a selective noncompetitive antagonist at the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, is highly effective in a wide range of experimental models. Although initially licensed as adjunctive therapy for partial seizures with or without secondary generalization in patients aged 12 years or older, the US Food and Drug Administration has recently approved its use in the treatment of primary generalized tonic–clonic seizures (PGTCS). This paper reviews the pharmacokinetics, efficacy, and tolerability of perampanel as an antiepileptic drug.Results: After oral ingestion, perampanel is rapidly absorbed (Tmax, 0.5–2.5 hours), has a bioavailability of ~100%, and is highly protein bound (~95%) in plasma. It undergoes extensive (>90%) hepatic metabolism, primarily via cytochrome P450 3A4 (CYP3A4), with a half-life of 48 hours. Carbamazepine and other antiepileptic drugs can enhance its metabolism via induction of CYP3A4. Efficacy of perampanel in focal seizures has been extensively evaluated in Phase II and randomized, placebo-controlled Phase III trials. The efficacy in PGTCS has been reported in one class I study. In the treatment of focal seizures, perampanel showed significant dose-dependent median seizure reductions: 4 mg/d, 23%; 8 mg/d, 26%–31%; 12 mg/d, 18%–35%; and placebo, 10%–21%. The 50% responder rates were 15%–26%, 29%, 33%–38%, and 34%–36% for placebo, 4 mg/d, 8 mg/d, and 12 mg/d perampanel, respectively. Freedom from seizures was recorded in 0%–1.7% of the placebo group, 1.9% of the 2 mg group, 2.6%–4.4% of the 8 mg group, and 2.6%–6.5% of the 12 mg group. For PGTCS, the median seizure reduction was 76.5% for perampanel and 38.4% for placebo. The 50% responder rate was 64.2% for perampanel and 39.5% for placebo. Seizure freedom during maintenance phase was 30.9% for perampanel and 12.3% for placebo. Adverse effects included dose-dependent increases in the frequency of dizziness, somnolence, fatigue, irritability, falls, and probably nausea.Conclusion: Perampanel is effective in treating both partial-onset seizures and PGTCS.Keywords: perampanel, new antiepileptic drug, epilepsy, primary generalized seizures, pharmacokineticsBesag FMPatsalos PNDove Medical Pressarticleperampanelnew antiepileptic drugepilepsyprimary generalized seizurespharmacokineticsNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2016, Iss Issue 1, Pp 1215-1220 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	perampanel new antiepileptic drug epilepsy primary generalized seizures pharmacokinetics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	perampanel new antiepileptic drug epilepsy primary generalized seizures pharmacokinetics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Besag FM Patsalos PN Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures
description	Frank MC Besag,1–3 Philip N Patsalos4,51East London Foundation NHS Trust, 2Institute of Psychiatry, Psychology and Neuroscience, 3UCL School of Pharmacy, 4Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, NIHR University College London Hospitals Biomedical Research Centre, London, 5Epilepsy Society, Chalfont Centre for Epilepsy, Chalfont St Peter, UKBackground and purpose: Perampanel, a selective noncompetitive antagonist at the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, is highly effective in a wide range of experimental models. Although initially licensed as adjunctive therapy for partial seizures with or without secondary generalization in patients aged 12 years or older, the US Food and Drug Administration has recently approved its use in the treatment of primary generalized tonic–clonic seizures (PGTCS). This paper reviews the pharmacokinetics, efficacy, and tolerability of perampanel as an antiepileptic drug.Results: After oral ingestion, perampanel is rapidly absorbed (Tmax, 0.5–2.5 hours), has a bioavailability of ~100%, and is highly protein bound (~95%) in plasma. It undergoes extensive (>90%) hepatic metabolism, primarily via cytochrome P450 3A4 (CYP3A4), with a half-life of 48 hours. Carbamazepine and other antiepileptic drugs can enhance its metabolism via induction of CYP3A4. Efficacy of perampanel in focal seizures has been extensively evaluated in Phase II and randomized, placebo-controlled Phase III trials. The efficacy in PGTCS has been reported in one class I study. In the treatment of focal seizures, perampanel showed significant dose-dependent median seizure reductions: 4 mg/d, 23%; 8 mg/d, 26%–31%; 12 mg/d, 18%–35%; and placebo, 10%–21%. The 50% responder rates were 15%–26%, 29%, 33%–38%, and 34%–36% for placebo, 4 mg/d, 8 mg/d, and 12 mg/d perampanel, respectively. Freedom from seizures was recorded in 0%–1.7% of the placebo group, 1.9% of the 2 mg group, 2.6%–4.4% of the 8 mg group, and 2.6%–6.5% of the 12 mg group. For PGTCS, the median seizure reduction was 76.5% for perampanel and 38.4% for placebo. The 50% responder rate was 64.2% for perampanel and 39.5% for placebo. Seizure freedom during maintenance phase was 30.9% for perampanel and 12.3% for placebo. Adverse effects included dose-dependent increases in the frequency of dizziness, somnolence, fatigue, irritability, falls, and probably nausea.Conclusion: Perampanel is effective in treating both partial-onset seizures and PGTCS.Keywords: perampanel, new antiepileptic drug, epilepsy, primary generalized seizures, pharmacokinetics
format	article
author	Besag FM Patsalos PN
author_facet	Besag FM Patsalos PN
author_sort	Besag FM
title	Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures
title_short	Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures
title_full	Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures
title_fullStr	Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures
title_full_unstemmed	Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures
title_sort	clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/d67b18ba8ba34c7fa16d616bc275362a
work_keys_str_mv	AT besagfm clinicalefficacyofperampanelforpartialonsetandprimarygeneralizedtonicclonicseizures AT patsalospn clinicalefficacyofperampanelforpartialonsetandprimarygeneralizedtonicclonicseizures
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Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures

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