目的 研究健康中国人在空腹与餐后状态下单剂量口服酒石酸匹莫范色林胶囊的药动学特征，并评价该受试制剂与参比制剂的生物等效性及安全性。方法 采用单中心、单次给药、随机、开放、两周期、交叉试验设计，其中空腹试验纳入26例健康受试者，餐后试验纳入32例健康受试者；每周期受试者单次口服受试制剂或参比制剂34 mg，采用超高效液相色谱-串联质谱（UPLC-MS/MS）法测定服药后22个不同时间点的血药浓度，运用Phoenix WinNonlin 8.3.4软件计算主要药动学参数，采用SAS 9.4软件进行生物等效性评价。结果 空腹条件下，受试制剂与参比制剂的主要药动学参数如下：最大血药浓度（C_max）分别为（20.74± 4.71）、（21.15± 4.67） ng·mL^-1；药时曲线下面积（AUC_0～t）分别为（1 429.12± 495.86）、（1 495.77±523.56） ng·mL^-1·h； AUC_0～∞分别为（1 537.26±393.96）、（1 583.48±393.43） ng·mL^-1·h；两种制剂的C_max、AUC_0～t、AUC_0～∞几何均值比值及其90%置信区间，均落在80.00%～125.00%的生物等效性判定区间内。餐后条件下，受试制剂与参比制剂的主要药动学参数如下： C_max分别为（17.87± 3.62）、（18.99± 3.71） ng·mL^-1； AUC_0～t分别为（1 491.76± 380.25）、（1 536.67± 370.19） ng·mL^-1·h； AUC_0～∞分别为（1 537.26± 393.96）、（1 583.48± 393.43） ng·mL^-1·h；上述3项参数的几何均值比值及其90%置信区间，亦均在80.00%～125.00%的生物等效性区间内。安全性方面，空腹试验不良事件发生率为42.3%（11例/26例），餐后试验不良事件发生率为65.6%（21例/32例）；试验期间未发生严重不良事件，亦未出现可疑且非预期严重不良反应。结论 酒石酸匹莫范色林胶囊受试制剂与参比制剂在空腹和餐后条件下均具有生物等效性，且安全性良好。

Objective To investigate the pharmacokinetic characteristics of a single-dose oral administration of Pimavanserin tartrate Capsule in healthy Chinese individuals under fasting and postprandial states, and to evaluate the bioequivalence and safety of the test formulation compared with the reference formulation. Methods A single-center, single-dose, randomized, open, two-period, crossover trial design was adopted. Among them, 26 healthy subjects were included in the fasting test, and 32 healthy subjects were included in the postprandial test. Each subject took the test formulation or the reference formulation at a dose of 34 mg once per cycle. The blood drug concentration at 22 different time points after administration was determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The main pharmacokinetic parameters were calculated using Phoenix WinNonlin 8.3.4 software, and the bioequivalence was evaluated using SAS 9.4 software. Results Under fasting conditions, the main pharmacokinetic parameters of the test formulation and the reference formulation were as follows: the maximum blood drug concentration (C_max) was (20.74 ± 4.71) and (21.15 ± 4.67) ng·mL^-1, respectively; the area under the curve (AUC_0～t) was (1 429.12 ± 495.86) and (1 495.77 ± 523.56) ng·mL^-1·h, respectively; the AUC_0～∞ was (1 537.26 ± 393.96) and (1 583.48 ± 393.43) ng·mL^-1·h, respectively. The geometric mean ratios of C_max, AUC_0～t, and AUC_0～∞ and their 90% confidence intervals of the two formulations were all within the 80.00% to 125.00% bioequivalence judgment range. Under postprandial conditions, the main pharmacokinetic parameters of the test formulation and the reference formulation were as follows: the C_max was (17.87 ± 3.62) and (18.99 ± 3.71) ng·mL^-1, respectively; the AUC_0～t was (1 491.76 ± 380.25) and (1 536.67 ± 370.19) ng·mL^-1·h, respectively; the AUC_0～∞ was (1 537.26 ± 393.96) and (1 583.48 ± 393.43) ng·mL^-1·h, respectively. The geometric mean ratios of the above three parameters and their 90% confidence intervals were also within the 80.00% to 125.00% bioequivalence range. In terms of safety, the incidence of adverse events in the fasting test was 42.3% (11/26), and that in the postprandial test was 65.6% (21/32); no serious adverse events occurred during the trial, and no suspected and unexpected serious adverse reactions were reported. Conclusion The test formulation of Pimavanserin tartrate Capsule and the reference formulation have bioequivalence under both fasting and postprandial conditions, and are safe.

R965.1;R975.5

“十三五”国家科技重大专项一致性评价定向委托课题子课题（2017ZX09101001-002-004）； 2020年省发改委预算内基本建设资金项目（创新能力建设，2020C038-1）