哌柏西利胶囊的人体生物等效性研究  

Study on the bioequivalence of Palbociclib capsules in human

作　　者：王彦超 王倩 董继宁 郝颖翠 刘秀娟 龙春梅 赵可新 WANG Yanchao;WANG Qian;DONG Jining;HAO Yingcui;LIU Xiujuan;LONG Chunmei;ZHAO Kexin(PhaseⅠClinical Trial Laboratory,Hebei PetroChina Central Hospital,Hebei Langfang 065000,China)

机构地区：[1]河北中石油中心医院药物Ⅰ期临床试验研究室,河北廊坊065000

出　　处：《中国药房》2023年第12期1498-1502,共5页China Pharmacy

摘　　要：目的评价健康受试者空腹或餐后单次口服2种哌柏西利制剂的生物等效性。方法分别纳入24例(空腹试验)和20例(餐后试验)健康受试者,均分为2组。采用单中心、开放、单剂量、两制剂、两周期、两序列、交叉试验设计,两组受试者分别空腹或餐后口服受试制剂(国产哌柏西利胶囊)或参比制剂(原研哌柏西利胶囊),清洗期为14 d。分别于用药前后不同时间点采集血样,经前处理后,以哌柏西利-d8为内标,采用高效液相色谱-串联质谱法测定其体内哌柏西利的质量浓度,采用SAS V9.4软件计算药动学参数并进行生物等效性评价。结果在空腹状态下,受试制剂和参比制剂的c_(max)分别为(71.4±18.1)、(73.8±19.0)ng/mL,AUC_(0-t)分别为(1754±412)、(1793±448)h·ng/mL,AUC_(0-∞)分别为(1851±456)、(1887±478)h·ng/mL;在餐后状态下,受试制剂和参比制剂的c_(max)分别为(78.4±18.3)、(81.9±21.7)ng/mL,AUC_(0-t)分别为(1905±375)、(1932±318)h·ng/mL,AUC_(0-∞)分别为(2027±411)、(2050±342)h·ng/mL;两项试验上述参数几何均值比的90%置信区间均在可接受范围(80.00%~125.00%)内。空腹、餐后状态下,分别有9、8例受试者发生20、16次不良事件,但均未见严重不良事件发生。结论在空腹、餐后状态下,哌柏西利胶囊受试制剂与参比制剂生物等效,且安全性相当。OBJECTIVE To evaluate the bioequivalence of a single oral administration of two palbociclib preparations in healthy subjects under fasting and fed conditions.METHODS Twenty-four healthy subjects(fasting test)and twenty healthy subjects(fed test)were enrolled and divided into two groups.A single-center,open-label,single-dose,two-formulation,two-period,two-sequence and crossover trial was designed.The subjects in the two groups were given the test preparation(domestic Palbociclib capsules)or the reference preparation(original Palbociclib capsules)orally under fasting or fed conditions respectively followed by a 14-day washout period.The blood samples were collected at different time points before and after treatment.After pretreatment,the mass concentration of palbociclib in vivo was determined by high-performance liquid chromatography-tandem mass spectrometry with palbociclib-d8 as the internal standard.SAS V9.4 software was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence.RESULTS Under fasting condition,the c_(max) of the test preparation and the reference preparation were(71.4±18.1)and(73.8±19.0)ng/mL;AUC_(0-t) were(1754±412)and(1793±448)h·ng/mL;AUC0-∞were(1851±456)and(1887±478)h·ng/mL,respectively.Under fed condition,the c_(max) of the test preparation and the reference preparation were(78.4±18.3)and(81.9±21.7)ng/mL;AUC_(0-t) were(1905±375)and(1932±318)h·ng/mL;AUC_(0-∞) were(2027±411)and(2050±342)h·ng/mL,respectively.The 90%CI of the geometric mean ratio of the above parameters was within the acceptable range(80.00%-125.00%).Under fasting and fed conditions,there were 20 and 16 adverse events in 9 and 8 subjects,respectively,but no serious adverse event was observed.CONCLUSIONS Under the fasting and fed conditions,the test preparation and the reference preparation of Pibociclib capsules are bioequivalent and have comparable safety.

关 键 词：哌柏西利 生物等效性 安全性 服药时间 

分 类 号：R969.1[医药卫生—药理学]