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目的:研究非洛地平缓释片在中国健康人体内的药动学特征和生物等效性。方法:采用双周期、随机、交叉试验设计,22名健康男性受试者先后在空腹状态和餐后状态下随机交叉单剂量口服受试制剂和参比制剂10 mg,在不同时间点采集血浆样本,周期间的清洗期为14 d。采用LC-MS/MS法测定血浆中非洛地平浓度,计算主要药动学参数并评价两种非洛地平制剂的生物等效性。结果:空腹状态下受试制剂与参比制剂的主要药动学参数如下:t1/2分别为(12.96±6.75)h和(14.15±6.19)h,tmax分别为(3.41±1.32)h和(3.66±1.43)h,Cmax分别为(3.42±1.38)μg·L-1和(3.30±1.09)μg·L-1,AUC0-t分别为(43.24±14.52)μg·h·L-1和(40.84±13.05)μg·h·L-1,AUC0-∞分别为(47.60±20.38)μg·h·L-1和(46.44±19.30)μg·h·L-1;餐后状态下受试制剂与参比制剂的主要药动学参数如下:t1/2分别为(12.78±4.33)h和(12.11±7.44)h,tmax分别为(4.50±0.67)h和(4.41±1.22)h,Cmax分别为(7.92±2.88)μg·L-1和(7.74±2.81)μg·L-1,AUC0-t分别为(51.12±13.35)μg·h·L-1和(50.38±15.86)μg·h·L-1,AUC0-∞分别为(53.71±14.48)μg·h·L-1和(52.39±16.04)μg·h·L-1。空腹和餐后状态下,受试制剂与参比制剂经方差分析和双单侧t检验,主要药动学参数无显著性差异。结论:2种制剂在空腹和餐后2种状态下均生物等效;食物对非洛地平缓释片的药动学有明显的影响。
Objective: To study the pharmacokinetics and bioequivalence of felodipine sustained-release tablets in healthy Chinese. Methods: A two-cycle, randomized, crossover trial design was used. Twenty-two healthy male subjects were randomized to receive a single oral dose of 10 mg of the test and reference preparations in fasting and postprandial states, and plasma samples were taken at different time points , The cleaning period of the week is 14 days. The concentrations of felodipine in plasma were determined by LC-MS / MS, the main pharmacokinetic parameters were calculated and the bioequivalence of the two formulations of felodipine was evaluated. Results: The main pharmacokinetic parameters of test preparation and reference preparation in fasting state were as follows: t1 / 2 were (12.96 ± 6.75) h and (14.15 ± 6.19) h, tmax was (3.41 ± 1.32) 3.66 ± 1.43 h and Cmax were (3.42 ± 1.38) μg · L-1 and (3.30 ± 1.09) μg · L-1, respectively. The AUC0-t was (43.24 ± 14.52) μg · h · L-1 and 40.84 ± 13.05) μg · h · L-1 and AUC0-∞ were (47.60 ± 20.38) μg · h · L-1 and (46.44 ± 19.30) μg · h · L-1, respectively. The main pharmacokinetic parameters were as follows: t1 / 2 was (12.78 ± 4.33) h and (12.11 ± 7.44) h respectively, and tmax was (4.50 ± 0.67) h and (4.41 ± 1.22) h and AUC0-t were (51.12 ± 13.35) μg · h · L-1 and (50.38 ± 15.86) μg · h · L-1 and AUC0-∞ were (53.71 ± 14.48) μg · h · L-1 and (52.39 ± 16.04) μg · h · L-1, respectively. Fasting and postprandial state, the test preparation and reference preparation by ANOVA and double unilateral t test, the main pharmacokinetic parameters were not significantly different. CONCLUSION: The two preparations are bioequivalent in both fasting and postprandial states. Food has a significant effect on the pharmacokinetics of felodipine sustained-release tablets.