Qiu Bo, Song Haojing, Sun Xue, Ding Congyang, Du Runxuan, Bai Wanjun, Dong Zhanjun
Department of Pharmacy, Hebei General Hospital, Shijiazhuang, Hebei, China.
Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei, China.
Front Pharmacol. 2025 Jan 3;15:1511214. doi: 10.3389/fphar.2024.1511214. eCollection 2024.
This study evaluated the pharmacokinetic and safety profiles of generic and original blonanserin tablets under fasting and postprandial conditions, and the bioequivalence of two formulations to obtain sufficient evidence for abbreviated new drug application.
A randomized, open-label, two-period, two-sequence, self-crossover bioequivalence study was conducted to assess the bioequivalence of the test and reference blonanserin tablets under fasting and postprandial conditions. Eligible healthy individuals received a single 4-mg dose of either the test or reference blonanserin tablet, followed by a wash out period of 14 days. Serial blood samples were collected for up to 72 h after administration during each period, and the plasma concentrations of blonanserin were determined using a validated method. The non-compartmental method was used to calculate the primary pharmacokinetic parameters, and the geometric mean ratios for the PK parameters of the test drug to those of the reference drug, along with the corresponding 90% confidence intervals, were obtained for bioequivalence analysis. Throughout the study, a safety evaluation was conducted.
Under both fasting and postprandial conditions, the pharmacokinetic parameters of the test drug were found to be similar to those of the reference drug. The 90% confidence intervals (CIs) of the geometric mean ratios of the test to reference formulations were 97.79%-118.28% for peak concentration (C), 92.35%-111.78% for the area under the curve from zero to the last measurable concentration (AUC) and 92.88%-111.91% for the AUC from zero to observed infinity (AUC) under fasting conditions, 88.65%-103.20% for C, 95.89%-106.81% for AUC and 96.02%-106.91% for AUC under postprandial conditions, all of which were within the accepted bioequivalence range of 80.00%-125.00%. Both the test and reference formulations were well-tolerated, and no serious adverse events related to the study drug were reported during the study.
The bioequivalence of blonanserin tablets, both test and reference, was confirmed in healthy Chinese subjects under fasting and postprandial conditions, meeting the predetermined regulatory criteria for both formulations. Both formulations were found to be safe and well tolerated.
http://www.chinadrugtrials.org.cn/index.html, identifier CTR20230703.
本研究评估了仿制药和原研布南色林片在空腹和餐后条件下的药代动力学及安全性概况，以及两种制剂的生物等效性，以为简略新药申请提供充分证据。
进行了一项随机、开放标签、两周期、两序列、自身交叉生物等效性研究，以评估受试布南色林片和参比布南色林片在空腹和餐后条件下的生物等效性。符合条件的健康个体单次服用4mg受试或参比布南色林片，随后有14天的洗脱期。在每个周期给药后最多72小时内采集系列血样，采用经过验证的方法测定血浆中布南色林的浓度。采用非房室模型法计算主要药代动力学参数，并获得受试药物与参比药物PK参数的几何平均比值及其相应的90%置信区间，用于生物等效性分析。在整个研究过程中进行了安全性评估。
在空腹和餐后条件下，受试药物的药代动力学参数均与参比药物相似。受试制剂与参比制剂几何平均比值的90%置信区间在空腹条件下，峰浓度（C）为97.79%-118.28%，从零至最后可测浓度的曲线下面积（AUC）为92.35%-111.78%，从零至观测到的无穷大的AUC为92.88%-111.91%；在餐后条件下，C为88.65%-103.20%，AUC为95.89%-106.81%，AUC为96.02%-106.91%，均在公认的80.00%-125.00%生物等效性范围内。受试制剂和参比制剂耐受性均良好，研究期间未报告与研究药物相关的严重不良事件。
在空腹和餐后条件下，健康中国受试者中受试布南色林片和参比布南色林片的生物等效性得到确认，符合两种制剂的预定监管标准。两种制剂均被发现安全且耐受性良好。
http://www.chinadrugtrials.org.cn/index.html，标识符CTR20230703。
