摘要
目的评价米拉贝隆缓释片受试制剂和参比制剂在空腹/餐后条件下的生物等效性。方法本试验用随机、开放、单剂量、四周期、两序列、自身交叉设计。空腹与餐后试验分别入组32例健康受试者,随机在空腹或餐后条件下口服米拉贝隆缓释片受试或参比制剂50 mg。用液相色谱串联质谱法测定血浆中米拉贝隆浓度,用Phoenix WinNonlin(8.2版本)软件计算药代动力学参数,并评价生物等效性。结果空腹试验米拉贝隆受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(43.91±21.40)和(40.82±24.94)ng·mL^(-1),AUC_(0-t)分别为(464.45±149.01)和(452.67±157.63)h·ng·mL^(-1),AUC_(0-∞)分别为(501.64±162.39)和(488.70±173.81)h·ng·mL^(-1)。餐后试验米拉贝隆受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(16.90±8.94)和(16.90±9.66)ng·mL^(-1),AUC_(0-t)分别为(247.09±82.53)和(243.22±78.20)h·ng·mL^(-1),AUC_(0-∞)分别为(269.58±86.52)和(265.66±81.89)h·ng·mL^(-1)。空腹和餐后试验,受试制剂与参比制剂AUC_(0-t)、AUC_(0-∞)和C_(max)几何均值比的90%置信区间均在80.00%~125.00%。结论米拉贝隆缓释片两制剂具有生物等效性。
Objective To evaluate the bioequivalence of test and reference mirabegron sustained release tablets under fasting/postprandial conditions.Methods A randomized,open,single dose,four cycle,two sequence,self-crossover trial design was used.32 healthy subjects respectively for fasting and fed study were enrolled,who were randomized to a single oral dose of 50 mg of either reference or test preparation of mirabegron sustained release tablets.The plasma concentration of mirabegron in healthy subjects after oral administration was detected by liquid chromatography tandem mass spectrometry,and Phoenix WinNonlin 8.2 software was used to calculate pharmacokinetic parameters and perform bioequivalence analysis.Results Subjects received a single oral dose of the reference and test formulations of mirabegron.The main pharmacokinetic parameters of mirabegron in the fasting study were asfollows:C_(max)were(43.91±21.40)and(40.82±24.94)ng·mL^(-1),AUC_(0-t)were(464.45±149.01)and(452.67±157.63)h·ng·mL^(-1)AUC_(0-∞)were(501.64±162.39)and(488.70±173.81)h·ng·mL^(-1).The main pharmacokinetic parameters of mirabegron in the fed study were as follows:C_(max)were(16.90±8.94)and(16.90±9.66)ng·mL^(-1),AUC_(0-t)were(247.09±82.53)and(243.22±78.20)h·ng·mL^(-1),AUC_(0-∞)were(269.58±86.52)and(265.66±81.89)h·ng·mL^(-1).The 90%confidence intervals for the geometric means of C_(max),AUC_(0-t)and AUC_(0-∞)for reference and test preparations in the fasting and fed groups were in the range of 80.00% to 125.00%.Conclusions The test and reference formulation of mirabegron sustained release tablets were bioeguivalence.
作者
杜晓琳
刘天美
朱祎婧
李潇
雍小兰
DU Xiao-lin;LIU Tian-mei;ZHU Yi-jing;LI Xiao;YONG Xiao-lan(Department of Pharmacy,Chengdu Xinhua Hospital,Chengdu 610066,Sichuan Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2024年第15期2246-2250,共5页
The Chinese Journal of Clinical Pharmacology
关键词
米拉贝隆缓释片
生物等效性
药代动力学
安全性
液相色谱串联质谱法
mirabegron sustained release tablet
bioequivalence
pharmacokinetics
safety
liquid chromatography tandem mass spectrometry
