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.