苯甲酸阿格列汀片在中国健康成年受试者中的生物等效性研究

Bioequivalence of alogliptin benzoate tablets in healthy Chinese adults

目的评价两种苯甲酸阿格列汀片在中国健康成年受试者中的安全性及生物等效性。方法采用开放、随机、单次给药、双周期交叉试验设计,入选28例与24例中国健康成年受试者,分别在空腹和餐后状态下单剂量口服苯甲酸阿格列汀片受试制剂和参比制剂各25mg,采用液相色谱串联质谱(LC-MS/MS)法测定受试者血浆中阿格列汀药物浓度,用Phoenix WinNonlin 8.0软件计算药代动力学参数,并用SAS 9.4软件进行生物等效性评价。结果受试者单次空腹口服受试制剂和参比制剂后血浆中阿格列汀的主要药代动力学参数:Cmax分别为(148.00±45.20),(151.00±46.10)ng·mL^-1,AUC0-t分别为(1650.05±212.47),(1626.16±236.34)ng·h·mL^-1,AUC0-∞分别为(1711.70±217.67),(1693.49±237.12)ng·h·mL^-1。T、R两制剂的Cmax、AUC0-t、AUC0-∞的几何均值比90%置信区间分别为90.12%~106.70%,100.03%~103.38%,99.85%~102.63%。单次餐后口服受试制剂和参比制剂后血浆中阿格列汀的主要药代动力学参数:Cmax分别为(179.00±57.20),(183.00±79.10)ng·mL^-1,AUC0-t分别为(1496.19±216.14),(1496.64±209.29) ng·h·mL^-1,AUC0-∞分别为(1554.20±227.43),(1549.99±218.81)ng·h·mL^-1。T、R两制剂的Cmax、AUC0-t、AUC0-∞的几何均值比90%置信区间分别为87.99%~113.28%,98.68%~101.35%,98.74%~101.61%。结论两种苯甲酸阿格列汀片在中国健康成年受试者体内生物等效。

Objective To evaluate the bioequivalence between two kinds of alogliptin benzoate tablets in healthy Chinese adults. Methods An open-label, randomized, single-dose, two-period, crossover study was conducted in 52 healthy Chinese adults under fasted(28 volunteers) or fed conditions(24 volunteers) conditions. All the volunteers were given single oral dose of alogliptin benzoate tablet 25 mg of test or reference formulation in each period. The plasma concentrations of alogliptin were determined by a validated LC-MS/MS method. The pharmacokinetic parameters were calculated by WinNonlin 8.0 software and the bioequivalence was evaluated by SAS 9.4 program. Results The main pharmacokinetic parameters of a single oral dose of alogliptin tablet under fasting condition for T and R were as follows: Cmax(148.00±45.20),(151.00±46.10) ng·mL^-1;AUC0-t(1650.05±212.47),(1626. 16 ± 236. 34) ng·h·mL^-1;AUC0-∞(1711. 70 ± 217. 67),(1693. 49 ± 237. 12) ng·h·mL^-1. The 90%confidential interval(CI) of geometric mean ratio for Cmax,AUC0-tand AUC0-∞were 90. 12%-106. 70%,100. 03%-103. 38%,99. 85%-102. 63%. The main pharmacokinetic parameters of a single oral dose of alogliptin tablet under fed condition for T and R were as follows: Cmax(179. 00 ± 57. 20),(183. 00 ± 79. 10) ng·mL^-1;AUC0-t(1496. 19 ± 216. 14),(1496. 64 ± 209. 29) ng·h·mL^-1;AUC0-∞(1554. 20 ± 227. 43),(1549. 99 ± 218. 81)ng·h·mL^-1. The 90% CI of geometric mean ratio for Cmax,AUC0-tand AUC0-∞were 87. 99%-113. 28%,98. 68%-101. 35%,98. 74%-101. 61%. Conclusion The two formulations of alogliptin tablets were bioequivalent in healthy Chinese adults.