Pharmacokinetics of Perampanel in Danish Paediatric Patients With Epilepsy Based on Therapeutic Drug Monitoring

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Pediatric Neurology

Background:

• Perampanel is an anti-seizure medication (ASM) used in pediatric epilepsy.
• Understanding variability in perampanel serum concentrations is crucial for effective treatment.
• Inter- and intra-patient variability in perampanel levels can influence treatment outcomes.

Purpose of the Study:

• To quantify inter- and intra-patient variability in serum perampanel concentrations.
• To assess the predictive value of perampanel concentrations for treatment efficacy and tolerability in pediatric patients.
• To identify factors influencing perampanel pharmacokinetics, such as age and co-medications.

Main Methods:

• Retrospective cohort study of 68 children and adolescents (<18 years) treated with perampanel.
• Analysis of 311 therapeutic drug monitoring (TDM) samples.
• Evaluation of dose-normalized concentration ratio (C:(D/kg)) by age group and co-medication category (enzyme-inducing ASMs, valproate, non-inducing ASMs).

Main Results:

• Perampanel concentrations were outside the recommended therapeutic range in 13.8% of samples.
• A 59.2-fold variation in C:(D/kg) was observed across patients.
• Younger children (<6 years) had lower concentrations than older adolescents (>12 years).
• Enzyme-inducing ASMs significantly reduced C:(D/kg).
• While 80.9% of patients showed reduced seizure burden and 20.6% achieved seizure freedom, serum concentrations did not correlate with these outcomes or adverse effects.

Conclusions:

• Therapeutic drug monitoring (TDM) is valuable for identifying under- or over-dosing of perampanel in pediatric patients.
• Age-related clearance changes and enzyme-inducing co-medications significantly affect perampanel concentrations.
• While serum concentrations can guide dose adjustments, optimization should focus on clinical seizure reduction and tolerability.