Plasma concentration and clinical effects of perampanel—The Kork experience

Abstract

A B S T R A C TPurpose: To investigate the correlation between steady-state plasma concentrations of perampanel (PER) with efficacy and tolerability in adult patients with difficult-to-treat epilepsy. Methods: PER plasma concentrations were assessed at steady-state conditions in 92 adult patients (57% female, 43% male, mean age 39,5 years, age range 20-73 years). All patients had been treated with PER at a stable dose for at least 3 weeks. Clinical efficacy was assessed on the day of measuring the plasma concentrations by a retrospective analysis of the seizure frequency and adverse effects. Results: The mean overall plasma concentration was 323,5 ng/ml (range 19 ng/ml -2436 ng/ml). The corresponding mean dose was 7,5 mg (range 2 mg -12 mg). PER dose and plasma concentration showed a close linear correlation. Plasma levels and doses varied widely concerning both efficacy and tolerability of PER. The differences between plasma levels of responders and non-responders were not statistically significant. Therefore a clinically useful general reference range could not be defined. Conclusion: Our data do not indicate a reliable therapeutic range for PER plasma concentrations. Individual reference ranges varied widely. Therapeutic drug monitoring (TDM) may still be helpful in certain clinical situations.

Pharmacokinetics, tolerability, and clinical effectiveness of perampanel in Japanese patients with epilepsy

“…In our previous study of perampanel treatment in 215 patients [3], the mean serum concentration in the 21 patients who achieved better outcomes was 450 ng/mL. In contrast, Steinhoff et al [10] evaluated 92 adult patients and found no significant differences between the plasma levels of responders and nonresponders.…”

Differential acute impact of therapeutically effective and overdose concentrations of lithium on human neuronal single cell and network function

“…In detail, data obtained from the clinical trial phase 3 showed that patients treated efficiently with Perampanel show a blood concentration in the range from 212 to 358 ng/mL (0.61–1.01 µM, with a 4 mg daily dose) and from 275 to 456 ng/mL (0.79–1.31 µM, with a 6 mg daily dose) 38 , 39 . Recent clinical data showed an even broader range of required blood levels of Perampanel to achieve effectiveness in patients 40 , 41 . Since more than 90% of Perampanel is bound by proteins 38 , 39 , the free Perampanel blood concentration is in the nanomolar range indicating that human brain AMPA receptor activity must be effectively modulated by Perampanel concentration in the nanomolar range.…”

The Effectiveness of Perampanel for Myoclonic Seizures in Down Syndrome with Isodicentric Chromosome 21

“…However, a reliable therapeutic range for the plasma concentration of perampanel has not been established because individual reference ranges vary widely [11]. According to previously reported data [12], in 92 adult patients at steady state, the mean overall plasma concentration of perampanel was 323.5 ng/mL. The corresponding mean dose was 7.5 mg (range 2–12 mg).…”