PMID- 32858369
OWN - NLM
STAT- MEDLINE
DCOM- 20210414
LR  - 20211204
IS  - 1525-5069 (Electronic)
IS  - 1525-5050 (Linking)
VI  - 112
DP  - 2020 Nov
TI  - Relationship between plasma concentrations and clinical effects of perampanel: A 
      prospective observational study.
PG  - 107385
LID - S1525-5050(20)30564-3 [pii]
LID - 10.1016/j.yebeh.2020.107385 [doi]
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) 
      [(mug/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.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Contin, Manuela
AU  - Contin M
AD  - IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department 
      of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. 
      Electronic address: manuela.contin@unibo.it.
FAU - Pondrelli, Federica
AU  - Pondrelli F
AD  - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 
      Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center, 
      (Reference Center for Rare and Complex Epilepsies - EpiCARE), Bologna, Italy.
FAU - Muccioli, Lorenzo
AU  - Muccioli L
AD  - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 
      Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center, 
      (Reference Center for Rare and Complex Epilepsies - EpiCARE), Bologna, Italy.
FAU - Mohamed, Susan
AU  - Mohamed S
AD  - IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
FAU - Santucci, Margherita
AU  - Santucci M
AD  - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 
      Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center, 
      (Reference Center for Rare and Complex Epilepsies - EpiCARE), Bologna, Italy.
FAU - Ferri, Lorenzo
AU  - Ferri L
AD  - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 
      Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center, 
      (Reference Center for Rare and Complex Epilepsies - EpiCARE), Bologna, Italy.
FAU - Licchetta, Laura
AU  - Licchetta L
AD  - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 
      Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center, 
      (Reference Center for Rare and Complex Epilepsies - EpiCARE), Bologna, Italy.
FAU - Tinuper, Paolo
AU  - Tinuper P
AD  - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 
      Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center, 
      (Reference Center for Rare and Complex Epilepsies - EpiCARE), Bologna, Italy.
FAU - Bisulli, Francesca
AU  - Bisulli F
AD  - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 
      Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center, 
      (Reference Center for Rare and Complex Epilepsies - EpiCARE), Bologna, Italy.
CN  - Perampanel Study Group
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20200825
PL  - United States
TA  - Epilepsy Behav
JT  - Epilepsy & behavior : E&B
JID - 100892858
RN  - 0 (Anticonvulsants)
RN  - 0 (Nitriles)
RN  - 0 (Pyridones)
RN  - H821664NPK (perampanel)
SB  - IM
MH  - Adult
MH  - *Anticonvulsants/therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nitriles
MH  - Plasma
MH  - Prospective Studies
MH  - *Pyridones/therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - Antiseizure medication
OT  - Efficacy
OT  - Epilepsy
OT  - Perampanel
OT  - Plasma concentration
OT  - Tolerability
COIS- 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.
FIR - Ambrosetti, Irene
IR  - Ambrosetti I
IRAD- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 
      Italy.
FIR - Boni, Antonella
IR  - Boni A
IRAD- IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center- Reference 
      Center for Rare and Complex Epilepsies - EpiCARE, Bologna, Italy.
FIR - Messana, Tullio
IR  - Messana T
IRAD- IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center- Reference 
      Center for Rare and Complex Epilepsies - EpiCARE, Bologna, Italy.
FIR - Michelucci, Roberto
IR  - Michelucci R
IRAD- IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center- Reference 
      Center for Rare and Complex Epilepsies - EpiCARE, Bologna, Italy.
FIR - Mostacci, Barbara
IR  - Mostacci B
IRAD- IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center- Reference 
      Center for Rare and Complex Epilepsies - EpiCARE, Bologna, Italy.
FIR - Parmeggiani, Antonia
IR  - Parmeggiani A
IRAD- Department of Medical and Surgical Sciences, University of Bologna, Bologna, 
      Italy.
FIR - Passarelli, Daniela
IR  - Passarelli D
IRAD- Faenza Hospital Unit, Azienda USL di Romagna, Faenza, Italy.
FIR - Rizzi, Romana
IR  - Rizzi R
IRAD- Department of Neuro-Motor Diseases, IRCCS Arcispedale Santa Maria Nuova, Reggio 
      Emilia, Italy.
FIR - Russo, Angelo
IR  - Russo A
IRAD- IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center- Reference 
      Center for Rare and Complex Epilepsies - EpiCARE, Bologna, Italy.
FIR - Volpi, Lilia
IR  - Volpi L
IRAD- IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
EDAT- 2020/08/29 06:00
MHDA- 2021/04/15 06:00
CRDT- 2020/08/29 06:00
PHST- 2020/06/25 00:00 [received]
PHST- 2020/07/27 00:00 [revised]
PHST- 2020/07/27 00:00 [accepted]
PHST- 2020/08/29 06:00 [pubmed]
PHST- 2021/04/15 06:00 [medline]
PHST- 2020/08/29 06:00 [entrez]
AID - S1525-5050(20)30564-3 [pii]
AID - 10.1016/j.yebeh.2020.107385 [doi]
PST - ppublish
SO  - Epilepsy Behav. 2020 Nov;112:107385. doi: 10.1016/j.yebeh.2020.107385. Epub 2020 
      Aug 25.