哌柏西利胶囊空腹和餐后给药人体生物等效性研究  

Bioequivalence study of palbociclib capsules in human under fasting and postprandial conditions

作　　者：王倩 潘静 樊雪艳 张丽丽 陈治松 董继宁 赵可新 王彦超 Qian WANG;Jing PAN;Xue-Yan FAN;Li-Li ZHANG;Zhi-Song CHEN;Ji-Ning DONG;Ke-Xin ZHAO;Yan-Chao WANG(Department of Pharmacy,Hebei Petrochina Central Hospital,Langfang 065000,Hebei Province,China)

机构地区：[1]河北中石油中心医院药学部,河北廊坊065000

出　　处：《药物流行病学杂志》2023年第10期1104-1112,共9页Chinese Journal of Pharmacoepidemiology

摘　　要：目的评价哌柏西利胶囊受试制剂(T)和参比制剂(R)在中国健康受试者空腹和餐后状态下的生物等效性和安全性。方法采用单中心、随机、开放、两制剂、两序列、两周期的交叉试验设计,空腹试验和餐后试验分别入组32例和28例健康受试者,受试者随机分配到2个试验组(T-R组和R-T组),每周期给药1次,125 mg/次。采用HPLC-MS/MS法测定血浆中哌柏西利浓度,用Phoenix Win Nonlin 8.3软件得出PK参数集,由非房室模型计算各受试者体内哌柏西利胶囊的药动学参数,进行统计分析,并对受试者的临床观察指标进行安全性评价。结果空腹试验和餐后试验分别有31例和28例受试者完成两个周期给药。受试者空腹和餐后状态下服用哌柏西利胶囊受试制剂和参比制剂的血浆药物最大浓度(C_(max))、时间-浓度曲线下面积(AUC_(0-t)和AUC_(0-∞))的几何均值比值的90%置信区间均在80.00%~125.00%范围内,两制剂生物等效。整个试验过程中未发生任何严重不良事件。结论受试制剂和参比制剂在中国健康志愿者空腹和进食条件下均具有生物等效性,且安全性良好。Objective To evaluate the bioequivalence and safety of the test and reference preparations of palbociclib capsules in Chinese healthy subjects under fasting and postprandial conditions.Methods A single-center,randomized,open-label,two-drug,two-sequence and two-cycle crossover trial was designed.32 healthy subjects were enrolled in the fasting trial and 28 healthy subjects were enrolled in the postprandial trial.The subjects were randomly assigned to two experimental groups(T-R group and R-T group),with a weekly administration of 125 mg each time.The concentration of palbociclib in plasma was determined by HPLC-MS/MS.The PK parameter set was obtained by Phoenix WinNonlin 8.3 software.The pharmacokinetic parameters of palbociclib capsules in each subject were calculated by noncompartmental model and statistically analyzed.The safety of clinical observation indexes of subjects was also evaluated.Results In the fasting and postprandial trials,31 and 28 subjects completed two cycles of dosing,respectively.The 90%confidence intervals of the geometric mean ratios of C_(max),AUC_(0-t) and AUC_(0-∞)of the test preparation and the reference preparation were in the range of 80.00%-125.00%,and the two preparations were bioequivalent after taking palbociclib capsules under fasting and postprandial conditions.No serious adverse events occurred throughout the trial.Conclusion The test and reference preparations of palbociclib capsules have bioequivalence and good safety in healthy Chinese volunteers under fasting and postprandial conditions.

关 键 词：哌柏西利 生物等效性 高效液相色谱-串联质谱 药代动力学 安全性 

分 类 号：R969[医药卫生—药理学]