克立硼罗软膏在健康受试者中的生物等效性研究  

Bioequivalence study of Crisaborole Ointments in healthy subjects

作　　者：刘伟 赖建明 于文雪 焦育红 陈桂玲 张晶波 LIU Wei;LAI Jianming;YU Wenxue;JIAO Yuhong;CHEN Guiling;ZHANG Jingbo(Jiangxi Kerui Pharmaceutical Industry Co.,Ltd.,Ganzhou 341008,China;Shulan(Hang Zhou)Hospital,Hangzhou 330000,China)

机构地区：[1]江西科睿药业有限公司,江西赣州341008 [2]树兰(杭州)医院,浙江杭州330000

出　　处：《现代药物与临床》2024年第12期3086-3093,共8页Drugs & Clinic

摘　　要：目的比较克立硼罗软膏受试制剂与参比制剂在健康受试者中单次局部外用后的生物等效性。方法采用随机、开放、两制剂、单次给药、双交叉设计。受试者于每周期在空腹状态下单次局部外用克立硼罗软膏受试制剂或参比制剂4 g(约5 mg/cm^(2)),清洗期为4 d。采用高效液相色谱-串联质谱法(HPLC-MS/MS)测定人血浆中克立硼罗的血药浓度,使用Phoenix Win Nonlin软件(8.3版本)中的非房室模型(NCA)模块计算克立硼罗的药动学参数。结果单次给药后,克立硼罗的C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比(受试制剂/参比制剂)的90%置信区间均在80.00%~125.00%。结论克立硼罗软膏受试制剂与参比制剂在健康受试者空腹条件下单次局部外用4 g(约5 mg/cm^(2))后具有生物等效性。Objective To compare the bioequivalence of the test formulation and the reference formulation of Crisaborole Ointments in healthy subjects after single topical dosage.Methods A randomized,open-label,two-treatment,single-dose,and two-way crossover design was adopted.Subjects were locally applied with 4 g(5 mg/cm^(2))Crisaborole Ointments test or reference preparation under fasting condition in each period,and the washout period was 4 d.The concentrations of crisaborole in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters of crisaborole were calculated using noncompartmental analysis model(NCA)in Phoenix WinNonlin software(version 8.3).Results After a single fasting administration,the 90%confidence intervals of the geometric mean ratios(the test formulation/reference formulation)of C_(max),AUC_(0-t),and AUC0-∞of crisaborole fell within the bioequivalent range of 80.00%to 125.00%.Conclusion The test and reference preparations of Crisaborole Ointments are bioequivalent in healthy subjects after single topical dosage of 4 g(5 mg/cm^(2))under fasting condition.

关 键 词：克立硼罗软膏 克立硼罗 药动学 生物等效性 HPLC-MS/MS 

分 类 号：R986[医药卫生—药品]