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

We aimed to quantify inter- and intra-patient variability in serum perampanel concentrations and assess whether concentrations predict efficacy or tolerability. We conducted a retrospective cohort study of 68 children and adolescents (< 18 years) treated at the Danish Epilepsy Centre (2017-2024), analysing 311 TDM samples. Dose-normalized concentration ratio was summarized as the concentration-to-dose-per-kilogram ratio (C:(D/kg)) and evaluated by age group and co-medication category: enzyme-inducing anti-seizure medications (ASMs), valproate or non-inducing ASMs. Clinical outcomes were change in seizure burden, seizure freedom and adverse effects. Perampanel concentrations were outside the recommended therapeutic range in 13.8% of samples, and C:(D/kg) varied 59.2-fold across patients. Children < 6 years had lower concentration than adolescents > 12 years, and enzyme-inducing ASMs markedly reduced C:(D/kg). Overall, 80.9% of patients had reduced seizure burden, and 20.6% became seizure-free, but serum concentrations did not correlate with seizure freedom or adverse effects. TDM is valuable for detecting under- or over-dosing caused by age-related clearance changes or enzyme-inducing co-medications. While dose adjustments can be guided by serum concentrations, optimization should ultimately target clinical seizure reduction and tolerability.