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Title: | Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy | Authors: | Silva, Rui Colom, Helena Bicker, Joana Almeida, Anabela Silva, Ana Sales, Francisco Santana, Isabel Falcão, Amílcar Fortuna, Ana |
Keywords: | perampanel; epilepsy; population pharmacokinetics; NONMEM; therapeutic drug monitoring | Issue Date: | 10-Jun-2023 | Publisher: | MDPI | Project: | POCI-01-0145-FEDER-030478 | Serial title, monograph or event: | Pharmaceutics | Volume: | 15 | Issue: | 6 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/113136 | ISSN: | 1999-4923 | DOI: | 10.3390/pharmaceutics15061704 | Rights: | openAccess |
Appears in Collections: | I&D ICNAS - Artigos em Revistas Internacionais I&D CIBIT - Artigos em Revistas Internacionais FFUC- Artigos em Revistas Internacionais |
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Population-Pharmacokinetic-Analysis-of-Perampanel-in-Portuguese-Patients-Diagnosed-with-Refractory-EpilepsyPharmaceutics.pdf | 6.11 MB | Adobe PDF | View/Open |
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