Perampanel for epilepsy with partial-onset seizures: a pharmacokinetic and pharmacodynamic evaluation

Abstract

Introduction: Epilepsies are among the most common diseases of the CNS. As available antiepileptic drugs do not successfully control seizures in one-third of these patients, the development of drugs with new mechanisms of action is an urgent requirement.

Areas covered: Preclinical and clinical data of the recently released antiepileptic drug perampanel are reviewed based on search in medical databases with special reference to its mechanism of action and to its pharmacokinetic properties relevant for clinical treatment. Pharmacodynamically, perampanel is a noncompetitive AMPA-receptor antagonist exerting its antiepileptic properties by modulating glutamatergic synaptic excitation. Pharmacokinetically, perampanel is characterized by a short T_max but slow hepatic metabolism and a mean plasma half-life of 105 h, allowing for once-daily dosing. Perampanel has shown antiepileptic properties in several animal models of seizures and epilepsy, and in clinical studies significantly reducing partial-onset seizures in a dose range from 4 to 12 mg/day both in blinded short-term and in open-label long-term extension trials even in highly pharmacoresistant patients. Aside from adverse effects of dizziness and somnolence, neuropsychiatric disturbances have been reported in patient subgroups, making careful clinical monitoring during uptitration recommendable.

Expert opinion: The use of perampanel focusing on control of abnormal synaptic excitation profits from favorable pharmacokinetics and from proven efficacy and overall good tolerability also in patient populations nonresponsive to treatment with previously available antiepileptic drugs.

Keywords:

• AMPA receptor
• antiepileptic drug
• epilepsy
• perampanel
• pharmacodynamics
• pharmacokinetics

Declaration of interests

The author is supported by grants from the German Research Foundation (Exzellenzinitiative). The author has received honoraria from pharmaceutical companies (Desitin, Eisai, UCB). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

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