目的 考察在空腹、餐后條件下健康受試者口服吡侖帕奈片受試制劑和參比制劑體內(nèi)吡侖帕奈的血藥濃度和藥動(dòng)學(xué)參數(shù)，評(píng)價(jià)吡侖帕奈片的生物等效性和安全性。方法 采用健康受試者在空腹、餐后的單中心、單劑量、兩制劑、隨機(jī)、開放、兩周期、自身交叉對(duì)照試驗(yàn)設(shè)計(jì)的人體生物等效性研究。空腹和餐后組健康受試者分別口服4 mg吡侖帕奈片受試制劑或參比制劑，采用HPLC-MS/MS法測(cè)定血漿中吡侖帕奈的濃度，藥動(dòng)學(xué)使用Phoenix WinNonlin 8.1軟件的非房室模型計(jì)算各受試者的藥動(dòng)學(xué)參數(shù)，使用SAS 9.4軟件進(jìn)行臨床安全性統(tǒng)計(jì)分析。結(jié)果 空腹、餐后試驗(yàn)吡侖帕奈片受試試劑和參比試劑的最大血藥濃度（C_max）分別為（181.20±46.14）、（168.60±47.98），(130.44±28.59)、（139.15±39.99）ng/mL，藥時(shí)曲線面積（AUC_0-t）分別為（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。兩組吡侖帕奈片兩種制劑的主要藥動(dòng)學(xué)參數(shù)幾何均值均在生物等效性80.00%～125.00%。空腹試驗(yàn)組和餐后試驗(yàn)組不良事件發(fā)生率分別為46.70%、50.00%，未出現(xiàn)嚴(yán)重不良事件。結(jié)論 吡侖帕奈片受試制劑和參比制劑具有生物等效性，單次服用安全且耐受性良好。

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.

R969.1