Cargando…

Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy

Perampanel is a promising antiepileptic drug (AED) for refractory epilepsy treatment due to its innovative mechanism of action. This study aimed to develop a population pharmacokinetic (PopPK) model to be further used in initial dose optimization of perampanel in patients diagnosed with refractory e...

Descripción completa

Detalles Bibliográficos
Autores principales: Silva, Rui, Colom, Helena, Bicker, Joana, Almeida, Anabela, Silva, Ana, Sales, Francisco, Santana, Isabel, Falcão, Amílcar, Fortuna, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302681/
https://www.ncbi.nlm.nih.gov/pubmed/37376153
http://dx.doi.org/10.3390/pharmaceutics15061704
_version_ 1785065100965576704
author Silva, Rui
Colom, Helena
Bicker, Joana
Almeida, Anabela
Silva, Ana
Sales, Francisco
Santana, Isabel
Falcão, Amílcar
Fortuna, Ana
author_facet Silva, Rui
Colom, Helena
Bicker, Joana
Almeida, Anabela
Silva, Ana
Sales, Francisco
Santana, Isabel
Falcão, Amílcar
Fortuna, Ana
author_sort Silva, Rui
collection PubMed
description Perampanel is a promising antiepileptic drug (AED) for refractory epilepsy treatment due to its innovative mechanism of action. This study aimed to develop a population pharmacokinetic (PopPK) model to be further used in initial dose optimization of perampanel in patients diagnosed with refractory epilepsy. A total of seventy-two plasma concentrations of perampanel obtained from forty-four patients were analyzed through a population pharmacokinetic approach by means of nonlinear mixed effects modeling (NONMEM). A one-compartment model with first-order elimination best described the pharmacokinetic profiles of perampanel. Interpatient variability (IPV) was entered on clearance (CL), while the residual error (RE) was modeled as proportional. The presence of enzyme-inducing AEDs (EIAEDs) and body mass index (BMI) were found as significant covariates for CL and volume of distribution (V), respectively. The mean (relative standard error) estimates for CL and V of the final model were 0.419 L/h (5.56%) and 29.50 (6.41%), respectively. IPV was 30.84% and the proportional RE was 6.44%. Internal validation demonstrated an acceptable predictive performance of the final model. A reliable population pharmacokinetic model was successfully developed, and it is the first enrolling real-life adults diagnosed with refractory epilepsy.
format Online
Article
Text
id pubmed-10302681
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-103026812023-06-29 Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy Silva, Rui Colom, Helena Bicker, Joana Almeida, Anabela Silva, Ana Sales, Francisco Santana, Isabel Falcão, Amílcar Fortuna, Ana Pharmaceutics Article Perampanel is a promising antiepileptic drug (AED) for refractory epilepsy treatment due to its innovative mechanism of action. This study aimed to develop a population pharmacokinetic (PopPK) model to be further used in initial dose optimization of perampanel in patients diagnosed with refractory epilepsy. A total of seventy-two plasma concentrations of perampanel obtained from forty-four patients were analyzed through a population pharmacokinetic approach by means of nonlinear mixed effects modeling (NONMEM). A one-compartment model with first-order elimination best described the pharmacokinetic profiles of perampanel. Interpatient variability (IPV) was entered on clearance (CL), while the residual error (RE) was modeled as proportional. The presence of enzyme-inducing AEDs (EIAEDs) and body mass index (BMI) were found as significant covariates for CL and volume of distribution (V), respectively. The mean (relative standard error) estimates for CL and V of the final model were 0.419 L/h (5.56%) and 29.50 (6.41%), respectively. IPV was 30.84% and the proportional RE was 6.44%. Internal validation demonstrated an acceptable predictive performance of the final model. A reliable population pharmacokinetic model was successfully developed, and it is the first enrolling real-life adults diagnosed with refractory epilepsy. MDPI 2023-06-10 /pmc/articles/PMC10302681/ /pubmed/37376153 http://dx.doi.org/10.3390/pharmaceutics15061704 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Silva, Rui
Colom, Helena
Bicker, Joana
Almeida, Anabela
Silva, Ana
Sales, Francisco
Santana, Isabel
Falcão, Amílcar
Fortuna, Ana
Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy
title Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy
title_full Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy
title_fullStr Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy
title_full_unstemmed Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy
title_short Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy
title_sort population pharmacokinetic analysis of perampanel in portuguese patients diagnosed with refractory epilepsy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302681/
https://www.ncbi.nlm.nih.gov/pubmed/37376153
http://dx.doi.org/10.3390/pharmaceutics15061704
work_keys_str_mv AT silvarui populationpharmacokineticanalysisofperampanelinportuguesepatientsdiagnosedwithrefractoryepilepsy
AT colomhelena populationpharmacokineticanalysisofperampanelinportuguesepatientsdiagnosedwithrefractoryepilepsy
AT bickerjoana populationpharmacokineticanalysisofperampanelinportuguesepatientsdiagnosedwithrefractoryepilepsy
AT almeidaanabela populationpharmacokineticanalysisofperampanelinportuguesepatientsdiagnosedwithrefractoryepilepsy
AT silvaana populationpharmacokineticanalysisofperampanelinportuguesepatientsdiagnosedwithrefractoryepilepsy
AT salesfrancisco populationpharmacokineticanalysisofperampanelinportuguesepatientsdiagnosedwithrefractoryepilepsy
AT santanaisabel populationpharmacokineticanalysisofperampanelinportuguesepatientsdiagnosedwithrefractoryepilepsy
AT falcaoamilcar populationpharmacokineticanalysisofperampanelinportuguesepatientsdiagnosedwithrefractoryepilepsy
AT fortunaana populationpharmacokineticanalysisofperampanelinportuguesepatientsdiagnosedwithrefractoryepilepsy