他达拉非口溶膜在健康志愿者体内的药物动力学及相对生物利用度

Pharmacokinetics and Relative Bioavailability of Tadalafil Orodispersible Films in Healthy Volunteers

考察了国产他达拉非(1)口溶膜在中国健康男性志愿者体内的药物动力学特征及其相对于1片的生物利用度。空腹试验采用随机、开放、三周期、双重拉丁方交叉试验设计,36名健康志愿者按1∶1∶1随机接受1口溶膜(不饮水)、1口溶膜(饮水)或1片(饮水);餐后试验采用随机、开放、两周期、交叉试验设计,志愿者按1∶1随机接受1口溶膜(饮水)或1片(饮水)。采用LC-MS/MS法检测血浆中1的浓度,并应用Win Nonlin 8.1软件计算药动学参数,SAS 9.4软件进行统计分析。结果表明,与1片相比,空腹试验中1口溶膜的主要药动学参数(c_(max)、AUC_(0→t)和AUC_(0→∞))几何均数比值的90%置信区间均落在80%~125%;而餐后试验中,1口溶膜的c_(max)未落在80%~125%。由此可见,空腹条件下,1口溶膜在不饮水及饮水条件下与1片均具有生物等效性,而在餐后条件下不具有生物等效性。

The pharmacokinetic characteristics of domestically produced tadalafil(1)orodispersible films in healthy male Chinese volunteers and their relative bioavailability compared with tadalafil tablets were investigated.A randomized,open-label,3-period,Latin square crossover trial under fasting conditions was performed,and 36 volunteers were randomized 1∶1∶1 to receive single oral dose of 1 film without water,1 film or tablet with water.A randomized,open label,2-period crossover trial under fed conditions was also performed,and 32 volunteers were randomized 1∶1 to receive 1 film or tablet with water.A LC-MS/MS method was used to determine the concentration of 1 in plasma.Main pharmacokinetic parameters were calculated by WinNonlin 8.1 software and the statistical analysis was conducted with SAS 9.4 software.The results showed that compared with 1 tablet,the 90%confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters(c_(max),AUC_(0→t) and AUC_(0→∞))of the 1 film in the fasting state were within the range of 80%-125%.While the 90%confidence interval for the geometric mean ratio of cmax of the 1 film was not within the range of 80%-125%in the fed state.These results showed that 1 film(with or without water)was bioequivalent to 1 tablets under fasting conditions but not bioequivalent under fed conditions.