A Single- and Multiple-Dose Pharmacokinetic Study of Oral Perampanel in Healthy Chinese Subjects

• Published in: Clinical drug investigation Vol. 43; no. 3; pp. 155 - 165
• Main Authors: Jing, Shan, Shiba, Sari, Morita, Masafumi, Yasuda, Sanae, Lin, Yang
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2023; Springer Nature B.V
• Subjects: Adult; Area Under Curve; Beverages; Convulsions & seizures; Dose-Response Relationship, Drug; Drug dosages; East Asian People; Epilepsy; Healthy Volunteers; Humans; Informed consent; Internal Medicine; Medicine; Medicine & Public Health; NCT; NCT03424564; Nitriles - pharmacokinetics; Original; Original Research Article; Pharmacokinetics; Pharmacology/Toxicology; Pharmacotherapy; Pyridones - pharmacokinetics; Working hours; Asia; China; Europe
• ISSN: 1173-2563; 1179-1918; 1179-1918
• DOI: 10.1007/s40261-022-01241-8

Background and Objective Perampanel is a once-daily oral anti-seizure medication indicated for focal-onset seizures and generalized tonic-clonic seizures. This study investigated the single- and multiple-dose pharmacokinetics of perampanel in healthy Chinese adults. Methods Study 052 (NCT03424564) was a phase I, single-center, open-label, parallel-group study. In the single-dose part of the study, subjects received a single oral dose of perampanel 2, 4, or 8 mg. In the multiple-dose part, subjects received once-daily oral perampanel 2 mg on Days 1–7 and 4 mg on Days 8–21. Pharmacokinetic parameters were determined from perampanel plasma concentrations using non-compartmental analysis. Dose proportionality after single doses of perampanel was assessed. Safety and tolerability were evaluated. Results In the single-dose part ( N  = 30), median time to reach maximum concentration ( t max ) was 0.75–1.0 h, mean terminal elimination phase half-life ( t ½ ) was 85.6–122 h, mean maximum observed concentration ( C max ) was 77.9–276 ng/mL, and mean area under the concentration–time curve from time zero to time of the last quantifiable concentration (AUC (0-t) ) was 4070–15100 ng·h/mL. Single-dose pharmacokinetics were linear for perampanel 2–8 mg. In the multiple-dose part ( N  = 12), Day 21 steady-state (4 mg/day) parameters were median time at which the highest drug concentration occurs at steady state ( t ss,max ), 1.25 h; mean t ½ , 109 h; mean maximum observed concentration at steady state ( C ss,max ), 453 ng/mL; and mean area under the concentration–time curve over the dosing interval on multiple dosing (AUC (0- τ) ), 7540 ng·h/mL. For single- and multiple-dose perampanel, the most common treatment-emergent adverse events were dizziness and somnolence. Conclusions Single- and multiple-dose pharmacokinetics of perampanel in healthy Chinese adults revealed rapid perampanel absorption, slow elimination, and a linear relationship with single perampanel doses of 2–8 mg. Findings were consistent with previous studies of perampanel pharmacokinetics in other ethnic/racial populations of healthy subjects. Single and multiple doses of perampanel were generally safe and well tolerated. Clinical Trial Registration NCT03424564; registered February 2018.