Abstract
OBJECTIVE: This study aimed to investigate the efficacy and tolerability of perampanel (PER) therapy and to optimize a specific plasma reference range for PER in children. Another major aim was to evaluate the potential determinators of PER concentration. METHODS: Concentrations obtained from 80 children were analyzed for routine therapeutic drug monitoring (TDM) between 2021 and 2022. We retrospectively reviewed the clinical data of these patients and assessed the efficacy at 3 months after treatment initiation. Trough concentration-to-dose ratio (C(0) /Dose ratio) of PER was compared among patients on various potential influencing factors. RESULTS: A 3-month PER therapy produced a ≥50% reduction in seizure frequency in 58.8% of patients. Twelve patients reported at least one adverse effect (AE), mainly dizziness. The monitoring data showed that the median C(0) was 325.5 ng/mL. Under maintenance dosages, approximately 75% of the C(0) values were 180.0-610.0 ng/mL. The C(0) /Dose ratio in patients aged 1 to <4 was significantly lower by twofold than in those aged 4 to ≤12 years (P = 0.001). Enzyme-inducing ASMs (EIASMs) decreased the C(0) /Dose ratio of PER by 25.9% (P = 0.165). In addition, seizure frequency reduction in responders was achieved at a median PER C(0) value of 357 ng/mL, which was similar to the value of 314 ng/mL found in nonresponders (P = 0.288). No significant difference was found in PER C(0) values between patients with and without AEs (P = 0.082). SIGNIFICANCE: In this study, PER treatment showed acceptable efficacy and tolerance in Chinese children with epilepsy. Contributing factors like age to variable C(0) /Dose ratios were identified, and complex PER-ASMs interactions were observed. Notably, the reference range, that is, 180.0-610.0 ng/mL, for routine PER monitoring may be more applicable for them. Routine TDM should be considered a positive attempt to manage the effectiveness and safety of PER.