TY - JOUR
T1 - Relationship between plasma concentrations and clinical effects of perampanel
T2 - A prospective observational study
AU - on behalf of the Perampanel Study Group
AU - Contin, Manuela
AU - Pondrelli, Federica
AU - Muccioli, Lorenzo
AU - Mohamed, Susan
AU - Santucci, Margherita
AU - Ferri, Lorenzo
AU - Licchetta, Laura
AU - Tinuper, Paolo
AU - Bisulli, Francesca
AU - Ambrosetti, Irene
AU - Boni, Antonella
AU - Messana, Tullio
AU - Michelucci, Roberto
AU - Mostacci, Barbara
AU - Parmeggiani, Antonia
AU - Passarelli, Daniela
AU - Rizzi, Romana
AU - Russo, Angelo
AU - Volpi, Lilia
N1 - Ricercatore distaccato presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Licchetta Laura, Tinuper Paolo, Bisulli Francesca, Contin Manuela, Santucci Margherita)
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Antiseizure medication
KW - Efficacy
KW - Epilepsy
KW - Perampanel
KW - Plasma concentration
KW - Tolerability
UR - http://www.scopus.com/inward/record.url?scp=85089799251&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089799251&partnerID=8YFLogxK
U2 - 10.1016/j.yebeh.2020.107385
DO - 10.1016/j.yebeh.2020.107385
M3 - Article
C2 - 32858369
AN - SCOPUS:85089799251
VL - 112
JO - Epilepsy and Behavior
JF - Epilepsy and Behavior
SN - 1525-5050
M1 - 107385
ER -