枸橼酸西地那非口崩片在中国健康男性受试者中的生物等效性研究  

Bioequivalence study of sildenafil citrate orodispersible tablets in Chinese healthy male subjects

作　　者：康静粉 眭紫薇 宋浩静[2] 董占军[2] 刘晓宇 刘洋 盖树常 KANG Jing-fen;SUI Zi-wei;SONG Hao-jing;DONG Zhan-jun;LIU Xiao-yu;LIU Yang;GAI Shu-chang(Hebei Longhai Pharmaceutical Co.,Ltd.Shijiazhuang 052165,Hebei Province,China;PhaseⅠClinical Laboratory,Hebei General Hospital,Shijiazhuang 050051,Hebei Province,China)

机构地区：[1]河北龙海药业有限公司,河北石家庄052165 [2]河北省人民医院Ⅰ期临床研究室,河北石家庄050051

出　　处：《中国临床药理学杂志》2023年第21期3164-3168,共5页The Chinese Journal of Clinical Pharmacology

基　　金：河北省科技厅河北省创新能力提升计划基金资助项目(225A2702D)。

摘　　要：目的评价两种枸橼酸西地那非口崩片在中国健康男性受试者体内空腹状态下的生物等效性。方法采用单中心、随机、开放、两周期、自身交叉、单次给药的平均生物等效性研究设计。将40例健康男性受试者,按随机表分为2组,每周期分别口服受试制剂(T)和参比制剂(R)。用液相色谱串联质谱(LC-MS/MS)法检测血浆中西地那非及其代谢物N-去甲基西地那非的浓度。用WinNonlin 8.1软件计算主要药代动力学(PK)参数,并评价两制剂的生物等效性。结果40例受试者完成试验。口服受试制剂和参比制剂后,血浆中西地那非的主要PK参数如下:C_(max)分别为(220.74±80.72)和(226.67±91.39)ng·mL^(-1),AUC_(0-t)分别为(581.18±224.62)、(574.32±214.68)ng·mL^(-1)·h,AUC_(0-∞)分别为(592.90±231.02)和(585.43±220.44)ng·mL^(-1)·h。代谢产物N-去甲基西地那非主要PK参数如下:Cmax分别为(108.76±40.22)和(109.91±45.52)ng·mL^(-1),AUC_(0-t)分别为(393.81±166.98)和(374.57±156.68)ng·mL^(-1)·h,AUC_(0-∞)分别为(403.89±172.25)和(384.83±161.20)ng·mL^(-1)·h。受试制剂和参比制剂中西地那非C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比值的90%置信区间分别为99.54%(92.36%,107.29%)、101.18%(96.63%,105.95%)、101.26%(96.79%,105.94%),均落在80.00%~125.00%,表明空腹状态下,受试制剂和参比制剂枸橼酸西地那非口崩片50 mg具有生物等效性。结论两制剂在中国健康男性受试者中具有生物等效性且安全性良好。Objective To evaluate the bioequivalence of two kinds of sildenafil citrate orodispersible tablets in Chinese healthy male subjects under fasting state.Methods A single-center,randomized,open-label,two-period,self-crossover,single-dose average bioequivalence study design was adopted in the study.Forty healthy male subjects were divided into two groups according to the random table,and received single oral dose of test(T)and reference(R)preparation each cycle,respectively.The concentrations of sildenafil and N-desmethylsildenafil(the metabolite of sildenafil)in plasma were measured by liquid chromatography-mass spectrometry(LC-MS/MS).The main pharmacokinetic parameters were calculated by WinNonlin 8.1 software,and the bioequivalence of the two preparations was evaluated.Results Forty subjects completed the test.The main pha rm acokinetic parameters of sildenafil of the test and reference preparations were as follows:Cmax were(220.74±80.72)and(226.67±91.39)ng·mL^(-1),AUC_(0-t)were(581.18±224.62)and(574.32±214.68)ng·mL^(-1)·h,AUC_(0-∞)were(592.90±231.02)and(585.43±220.44)ng·mL^(-1)·h.For N-desmethylsildenafil(the metabolite of sildenafil),C_(max) were(108.76±40.22)and(109.91±45.52)ng·mL^(-1),AUC_(0-t) were(393.81±166.98)and(374.57±156.68)ng·mL^(-1)·h,AUC_(0-∞)were(403.89±172.25)and(384.83±161.20)ng·mL^(-1)·h.The 90%confidence intervals of geometric mean ratios of test and reference preparations were 99.54%(92.36%,107.29%)for the C_(max),101.18%(96.63%,105.95%)for the AUC_(0-t),and 101.26%(96.79%,105.94%)for the AUC_(0-∞),all of which were within 80.00%-125.00%,which indicating that the test and reference preparations of sildenafil citrate orodispersible tablets 50 mg were bioequivalent under fasting state.Conclusion The two preparations were bioequivalent and safe in Chinese healthy male subjects.

关 键 词：枸橼酸西地那非口崩片 液相色谱串联质谱 药代动力学 生物等效性 

分 类 号：R97[医药卫生—药品]