The practical impact of altered dosing on perampanel plasma concentrations: Pharmacokinetic modeling from clinical studies

The clinical pharmacology profile of the new antiepileptic drug perampanel: A novel noncompetitive AMPA receptor antagonist

“…For drugs with a longer half‐life, such as perampanel, it takes longer to reach steady‐state, since little drug is eliminated between doses and thus dosing intervals are longer. This characteristic may facilitate medication compliance by reducing the required frequency of dosing; if a dose is missed, a significant loss in coverage is not expected (see ). Furthermore, a long half‐life may minimize the peak‐to‐trough fluctuations and thus minimize the likelihood of underexposure and breakthrough seizures or overexposure and dose‐related toxicity; also, if absolutely needed, perampanel can be discontinued abruptly since blood levels fall gradually…”

“…Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with or without secondarily generalized seizures in patients with epilepsy aged ≥12 years have been established in a phase III clinical program . In addition, perampanel PKs have been extensively investigated in animal studies, in both single‐dose and multidose studies in healthy volunteers, and in patients with epilepsy who are receiving concomitant medications, and in different age groups . However, the overall clinical pharmacology and the implications of perampanel PKs in a clinical context have yet to be explored, and these data are now reviewed in this regard.…”

Comparative Bioavailability of Two Oral Perampanel Formulations in Healthy Subjects: A Randomized, Open Label, Single-Dose, 2-Way Crossover Study

“…Perampanel's coefficients of variations (CV) expressed as CV% in many single and multiple dose PK studies carried out in healthy subjects' range between 15% to 40% in relation to C max and the CV% of AUC inf is reported to vary from 30 to 60% after a single dose-dose administration [11,12]. Also, in epilepsy patients the variability of perampanel plasma concentrations is reported with an inter-individual CV of 132% [8]. In our study, the AUC 0-last was not truncated after the completion of distribution phase as it was done in some previous PK studies.…”

“…Several single and multi-dose Pharmacokinetics (PKs) studies have been conducted both in healthy subjects and in epilepsy patients [6,8]. Perampanel has a mean oral absolute bioavailability of 100%…”

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

“…Twice-daily dosing offers little advantage in reducing plasma concentration fluctuations, and a missed dose will induce only a minor reduction in the plasma profile [45]. This is of major advantage as T max -related side effects can be avoided with nightly administration and adherence to the intake is facilitated [46,47], and individual misses may have less severe impact on seizure control than with AED of short plasma half-time.…”