王秀英 1刘亚利 1李晓洁 1王少珊 1林莉 1杨珍珍 1吴库生2
作者信息
- 1. 汕头大学医学院第一附属医院药物Ⅰ期临床试验研究室,广东 汕头 515041
- 2. 汕头大学医学院公共卫生与预防医学教研室,广东 汕头 515041
- 折叠
摘要
Abstract
Objective:To evaluate the bioequivalence of two tenofovir alafenamide fumarate tablets administered orally to healthy subjects under fasting and fed conditions.Methods:42(fasting test)and 42(fed test)healthy subjects were enrolled in 2 groups.The fasting test was a non-replicated crossover design(two-cycle,two-sequence,two-crossover,single dose),and the fed test was a three-cycle partially replicated crossover design(three-cycle,three-sequence,three-crossover,single dose),and the two groups of subjects were given the test preparation(Tenofovir alafenamide fumarate tablets)or the reference preparation(Vemlidy)orally on a fasting or fed diet,with a washout period of 14 d.Blood samples were collected at different time points before and after drug administration,and the mass concentrations of tenofovir alafenamide and tenofovir in plasma were determined by high performance liquid chromatography-tandem mass spectrometry.Pharmacokinetic parameters of tenofovir alafenamide and tenofovir were calculated using WinNonlin 8.1 pharmacokinetic software for bioequivalence evaluation.Results:The 90%confidence intervals for the geometric mean ratios of cmax,AUC0-t,and AUC0-∞for tenofovir alafenamide in plasma after oral administration of the test and reference preparation to the subjects in the fasting state were 85.96%-115.23%,90.94%-109.08%,and 92.77%-111.10%,which were within an acceptable range(80.00%-125.00%).In the fed state,the 90%confidence intervals for the geometric mean ratios of AUC0-t and AUC0-∞ for tenofovir alafenamide were 87.83%-100.69%and 87.39%-99.77%,respectively,which were within the range of 80.00%-125.00%;and the point estimates of the geometric mean ratios of cmax were 80.92%-115.93%,which were within the range of 80.00%-125.00%range and the upper limit of the one-sided 95%confidence interval was less than zero.In the fasting and fed conditions,39 and 38 adverse events occurred in 20 and 26 subjects,respectively,but no serious adverse events occurred.Conclusion:The test preparation,tenofovir alafenamide fumarate tablets,was bioequivalent to the reference preparation and had a comparable safety profile in the fasting,fed conditions.关键词
富马酸丙酚替诺福韦片/生物等效性/安全性/丙酚替诺福韦Key words
tenofovir alafenamide fumarate tablets/bioequivalence/safety/tenofovir alafenamide分类
医药卫生
