厄贝沙坦片在中国健康人体内的生物等效性研究

Bioequivalence of irbesartan tablets in healthy Chinese subjects

目的研究厄贝沙坦片在中国健康人体内的生物等效性。方法采用单中心、随机、开放、单剂量、两周期、2×2交叉试验设计,空腹试验和餐后试验中分别有32例受试者口服厄贝沙坦片受试制剂或参比制剂0.15 g。LC-MS/MS法测定给药后不同时间厄贝沙坦的血药浓度,并用Phoenix WinNonlin 7.0软件计算主要药代动力学参数,判定两制剂是否等效。结果空腹试验受试制剂和参比制剂厄贝沙坦的主要药代动力学参数:C_(max)分别为(2242.4±631.5),(2327.3±821.0)ng·mL^(-1),AUC_(0-t)分别为(9953.2±3339.6),(10218.5±2985.3)h·ng·mL^(-1),AUC_(0-∞)分别为(10201.7±3377.9),(10516.5±2995.6)h·ng·mL^(-1),T_(max)均为1.50 h;t_(1/2)分别为(12.3±5.8),(15.1±10.3)h。餐后试验受试制剂和参比制剂厄贝沙坦的主要药代动力学参数:C_(max)分别为(2691.8±663.7),(2598.8±877.1)ng·mL^(-1),AUC_(0-t)分别为(10129.8±3783.9),(9538.6±3151.8)h·ng·mL^(-1),AUC_(0-∞)分别为(10353.1±3792.3),(9720.1±3162.0)h·ng·mL^(-1),T_(max)均为1.50 h;t_(1/2)分别为(12.5±7.6),(10.3±5.2)h。受试制剂与参比制剂C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比的90%置信区间均完全落在80.00%~125.00%。结论2种厄贝沙坦片在中国健康志愿者体内具有生物等效性。

Objective To study the bioequivalence of irbesartan tablets in healthy Chinese subjects.Methods With single-center,randomized,open,single-dose,two-cycle,two cross-over trial,fasting test in 32 healthy subjects and postprandial test in 32 healthy subjects,take irbesartan tablet test preparation 0.15 g or reference preparation 0.15 g orally.Determining the plasma concentrations of irbesartan at different time after treatment by LC-MS/MS,calculating the main pharmacokinetic parameters by Phoenix WinNonlin 7.0 to determine whether the two preparations were equivalent.Results The pharmacokinetic parameters of test preparation and reference preparation in fasting state were as follows:C_(max) were(2242.4±631.5)and(2327.3±821.0)ng·mL^(-1),AUC_(0-t) were(9953.2±3339.6)and(10218.5±2985.3)h·ng·mL^(-1),AUC_(0-∞)were(10201.7±3377.9)h·ng·mL^(-1)and(10516.5±2995.6)h·ng·mL^(-1),both of their T_(max) were 1.50 h,T_(1/2) were(12.3±5.8)and(15.1±10.3)h.The pharmacokinetic parameters of test preparation and reference preparation in postprandial state were as follows:C_(max) were(2691.8±663.7)and(2598.8±877.1)ng·m L^(-1),AUC_(0-t) were(10129.8±3783.9)h·ng·mL^(-1)and(9538.6±3151.8)h·ng·mL^(-1),AUC_(0-∞)were(10353.1±3792.3)and(9720.1±3162.0)h·ng·m L^(-1),both of their T_(max) were1.50 h,T_(1/2) were(12.5±7.6)and(10.3±5.2)h.The 90%confidence intervals of the geometric mean ratios of the test preparation and the reference preparation C_(max),AUC_(0-t) and AUC_(0-∞)were all completely fall within80.00%-125.00%.Conclusion The test and reference preparations of irbesartan were bioequivalent in Chinese healthy subjects.