吡仑帕奈片在健康受试者中的生物等效性研究

目的 考察在空腹、餐后条件下健康受试者口服吡仑帕奈片受试制剂和参比制剂体内吡仑帕奈的血药浓度和药动学参数，评价吡仑帕奈片的生物等效性和安全性。方法 采用健康受试者在空腹、餐后的单中心、单剂量、两制剂、随机、开放、两周期、自身交叉对照试验设计的人体生物等效性研究。空腹和餐后组健康受试者分别口服4 mg吡仑帕奈片受试制剂或参比制剂，采用HPLC-MS/MS法测定血浆中吡仑帕奈的浓度，药动学使用Phoenix WinNonlin 8.1软件的非房室模型计算各受试者的药动学参数，使用SAS 9.4软件进行临床安全性统计分析。结果 空腹、餐后试验吡仑帕奈片受试试剂和参比试剂的最大血药浓度（C_max）分别为（181.20±46.14）、（168.60±47.98），(130.44±28.59)、（139.15±39.99）ng/mL，药时曲线面积（AUC_0-t）分别为（7 587.46±2 975.40）、（7 485.88±2 910.03），（7 820.54±3 229.68）、（7 528.88±2 325.94）h·ng/mL。两组吡仑帕奈片两种制剂的主要药动学参数几何均值均在生物等效性80.00%～125.00%。空腹试验组和餐后试验组不良事件发生率分别为46.70%、50.00%，未出现严重不良事件。结论 吡仑帕奈片受试制剂和参比制剂具有生物等效性，单次服用安全且耐受性良好。

Bioequivalence of Perampanel Tablets in healthy subjects

Objective To investigate the plasma concentrations and pharmacokinetic parameters of perampanel in human body of healthy subjects po administered with the test and reference preparation of Perampanel Tablets under fasting and fed conditions, and to evaluate of the bioequivalence and safety of two preparations. Methods A single center, single dose, two preparations, randomized, open-label, two-cycle, and self-cross controlled trial design on bioequivalence of healthy subjects under fasting and fed conditions was studied. Subjects were po administered with the test or reference preparation of 4 mg Perampanel Tablets under both fasting and fed conditions, respectively. The concentration of perampanel in plasma was determined by LC-MS/MS method, the pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.1 in non-compartment model, and the statistical analysis of clinical safety were evaluated by SAS 9.4 software. Results The main pharmacokinetics parameters C_max and AUC_0-t of the test and reference preparation of Perampanel Tablets under fasting and fed conditions were as follows: (181.20 ± 46.14), (168.60 ± 47.98), and (130.44 ± 28.59) and (139.15 ± 39.99) ng/mL; (7 587.46 ± 2 975.40), (7 485.88 ± 2 910.03), and (7 820.54 ± 3 229.68), (7 528.88 ± 2 325.94) h·ng/mL. The geometric mean ratios of the main pharmacokinetic parameters of the two groups of Perampanel Tablets were 80.00%-125.00%. The incidence of adverse events in the fasting and fed conditions groups were 46.70% and 50.00%, respectively, and no serious adverse events occurred. Conclusion The test and reference preparation of Perampanel Tablets are bioequivalent, safe and well tolerated in a single dose.