Related Experiment Video
Updated: Jul 25, 2025

Electrophoretic Delivery of γ-aminobutyric Acid GABA into Epileptic Focus Prevents Seizures in Mice
Published on: May 16, 2019
Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy
Rui Silva1,2, Helena Colom3,4, Joana Bicker1,2
1Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
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.
Related Concept Videos
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Antiepileptic Drugs: Potassium Channel Activators
Ezogabine has gained approval as an adjunctive treatment...
Analysis of Population Pharmacokinetic Data
Noncompartmental Analysis: Miscellaneous Pharmacokinetic Parameters
One key aspect of the noncompartmental approach is determining a drug's total clearance. This can be done by dividing the drug dose by the area under the concentration-time curve from zero to infinity. The area under the concentration-time curve represents the drug's...
Depolarizing Blockers: Pharmocokinetics
Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...

