Relationship between plasma concentrations and clinical effects of perampanel: A prospective observational study.

Purpose: The purpose of the study was to investigate the potential correlation between plasma concentration of the newer antiseizure medication (ASM) perampanel (PMP) and both tolerability and seizure control in patients with epilepsy.
Methods: The study design was multicenter, open, and prospective. Plasma samples were collected in the morning 12 h apart from once-a-day bedtime PMP dose. Perampanel tolerability was assessed on the day of drug monitoring by clinical examination and patients' interview. Response to PMP was defined as ≥50% reduction from baseline seizure frequency (pretreatment). The main outcomes were the comparisons of PMP plasma concentration-to-weight-adjusted dose ratio (C/D) [(μg/mL)/(mg/kg/day)] between patients with and without PMP-related adverse effects (AEs) and between responders and nonresponders.
Results: Ninety-seven patients (54% men), mean ± SD age 36 ± 14 years were enrolled in the study. The mean PMP dose was 6.7 ± 2.3 mg, drug treatment averaged 46 ± 34 weeks. The mean plasma concentration was 360 ± 268 ng/mL (range: 37-1213 ng/mL). Forty patients (41%) reported at least one AE, mainly dizziness and behavioral changes. No significant difference was found in median PMP C/Ds between patients with (2.94) and without (2.76) AEs, otherwise comparable for clinical variables. Forty-four patients (45%) were responders, at a median PMP C/D of 3.10, similar to the value of 2.76 found in nonresponders. These two groups also overlapped for clinical characteristics.
Conclusion: This is the first prospective real-life study to evaluate the relationship between PMP plasma concentrations, seizure control, and AEs. In line with the few real-world available data, we did not find any significant correlation between PMP plasma concentrations and both tolerability and seizure control.
Competing Interests: Declaration of competing interest Dr. Bisulli has participated in clinical trials for GW; received research grants from Eisai; received support for travel to congresses from Cyberonics, Eisai, UCB and Bial; participated in advisory boards for Eisai and UCB; has received speaker honoraria from Eisai and UCB. Dr. Licchetta received support for travel to congresses from Eisai. Dr. Tinuper has participated in clinical trials for GW, UCB and LivaNova; received research grants from Eisai, UCB and Livanova; received support for travel to congresses from Cyberonics, Eisai, UCB and Bial; participated in advisory boards for Eisai, UCB, LivaNova and GW; has received speaker honoraria from Eisai, UCB and LivaNova. For the remaining authors none were declared.
(Copyright © 2020 Elsevier Inc. All rights reserved.)