他达拉非片在中国健康受试者中的人体生物等效性研究  

Bioequivalence of tadalafil tablets in healthy Chinese volunteers

作　　者：王敏 邵艳玲 张丽 冯松 刘佳琦 武艺伟 于宏坡 王红艳[3] 郎丽巍 朱姗薇 宋占东 龚明峰 赵攀 魏振满 朱珍真 WANG Min;SHAO Yan-ling;ZHANG Li;FENG Song;LIU Jia-qi;WU Yi-wei;YU Hong-po;WANG Hong-yan;LANG Li-wei;ZHU Shan-wei;SONG Zhan-dong;GONG Ming-feng;ZHAO Pan;WEI Zhen-man;ZHU Zhen-zhen(Phase I Clinical Trial Ward,The Fifth Medical Center of PLA General Hospital,Beijing 100039,China;Beijing Garrison Haidian 17th Retired Cadres Recuperation,Beijing 100036,China;Department of Pharmacy,Medical Supplies Center of PLA General Hospital,Beijing 100039,China;Yuanda Pharmaceutical(China)Co.,Ltd.,Wuhan 430000,Hubei Province,China)

机构地区：[1]中国人民解放军总医院第五医学中心Ⅰ期临床试验病房,北京100039 [2]北京卫戍区海淀第十七退休干部休养所,北京100036 [3]解放军总医院医疗保障中心药剂科,北京100039 [4]远大医药(中国)有限公司,湖北武汉430000

出　　处：《中国临床药理学杂志》2023年第16期2383-2387,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价2种他达拉非片在中国健康受试者的生物等效性及安全性。方法按单中心、开放、随机、单次给药、两制剂、两序列、两周期、交叉试验研究设计方法,空腹和餐后条件下分别入组28例男性健康受试者,随机交叉单次口服受试制剂和参比制剂5 mg,用HPLC-MS/MS法测定血浆中他达拉非的浓度,用Phoenix WinNonlin(6.4版本)软件计算他达拉非的药代动力学参数,并进行生物等效性评价。结果受试者服用受试制剂和参比制剂后,空腹组血浆中他达拉非的主要药代动力学参数如下:Cmax分别为(99.84±29.62)和(106.80±27.40)ng·mL^(-1);AUC_(0-t)分别为(2609.66±877.13)和(2617.84±967.29)ng·h·mL^(-1);AUC_(0-∞)分别为(2779.56±1043.90)和(2803.44±1281.10)ng·h·mL^(-1)。餐后组血浆中他达拉非的主要药代动力学参数如下:Cmax分别为(104.93±23.51)和(106.79±19.96)ng·mL^(-1);AUC_(0-t)分别为(2657.78±1096.81)和(2799.12±1074.22)ng·h·mL^(-1);AUC_(0-∞)分别为(2826.60±1321.58)和(3003.94±1352.96)ng·h·mL^(-1)。2种制剂的Cmax、AUC_(0-t)和AUC_(0-∞)经对数转换后90%可信区间分别为空腹状态下82.46%~100.42%、91.86%~108.48%、93.09%~110.40%;餐后状态下92.70%~104.48%、89.33%~98.95%、88.48%~98.42%。结论2种他达拉非片在中国健康男性受试者中具有生物等效性。Objective To evaluate the bioequivalence and safety of two kinds of tadalafil tablets in Chinese healthy volunteers.Methods A single-center,open-label,randomized,single-dose,two-preparation,two-sequence,two-cycle,cross-over study design was used.28 healthy subjects were enrolled under fasting and fed conditions,respectively.A single oral dose of 5 mg of the test preparation and the reference preparation was administered in a randomized crossover manner.The concentration of tadalafil in plasma was determined by HPLC-MS/MS.The pharmacokinetic parameters of tadalafil were calculated by Phoenix WinNonlin(version 6.4)software,and the bioequivalence was evaluated.Results The main pharmacokinetic parameters of tadalafil after administration of the test and reference preparations in fasting condition were as follows:Cmax were(99.84±29.62),(106.80±27.40)ng·mL^(-1);AUC_(0-t) were(2609.66±877.13),(2617.84±967.29)ng·h·mL^(-1);AUC_(0-∞)were(2779.56±1043.90),(2803.44±1271.10)ng·h·mL^(-1).In fed condition Cmax were(104.93±23.51),(106.79±19.96)ng·mL^(-1);AUC_(0-t) were(2657.78±1096.81),(2799.12±1074.22)ng·h·mL^(-1);AUC_(0-∞)were(2826.60±1321.58),(3003.94±1352.96)ng·h·mL^(-1).The 90%confidential intervals of Cmax,AUC_(0-t) and AUC_(0-∞)of tested formulation in the fasting state were 82.46%-100.42%,91.86%-108.48%,93.09%-110.40%;in the fed state,they were 92.70%-104.48%,89.33%-98.95%,88.48%-98.42%.Conclusion Two kinds of tadalafil tablets are bioequivalent in Chinese healthy male subjects.

关 键 词：他达拉非 药代动力学 血药浓度 生物等效性 

分 类 号：R97[医药卫生—药品]