Purpose: The present study aimed to establish and validate an isotope-dilution-UHPLC-MS/MS method for the determination of perampanel (PER) concentration and investigate the effect of eslicarbazepine acetate (ESL) on the pharmacokinetics of PER in rats.
Methods: The rats were randomly divided into the control (0.5% CMC-Na) and experimental groups (ESL, 72 mg/kg), with six rats in each group. A single dose of PER (1 mg/kg) was administered after a week of repetitive 0.5% CMC-Na or ESL dosing (72 mg/kg); then, plasma samples were collected. Perampanel-d (PER-d) was used as the internal standard (IS), liquid-liquid extraction of plasma samples was carried out using ethyl acetate, and chromatographic separation was carried out on a Titank C18 column (2.1 mm × 50 mm, 3.0 μm) using a gradient mobile phase consisting of 0.1% formic acid and acetonitrile at a flow rate of 0.3 mL/min.
Results: PER had good linearity (0.3-600 ng/mL, r >0.999), and the accuracy, precision, recovery rate, and matrix effects (ME) met the Food and Drug Administration (FDA) guidelines. Compared to the control group, the area under the curve AUC AUC, and Cmax of PER in the experimental group decreased by 30.28%, 30.34%, and 46.94%, respectively, and CL increased by 32.08%.
Conclusion: ESL could induce the metabolism of PER in rats and decreases plasma exposure to PER. Thus, the concomitant treatment with ESL may require a high dose of PER to achieve the same efficacy.
