Plasma concentration and clinical effects of perampanel-The Kork experience

Purpose: 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.