奥美拉唑肠溶胶囊高脂餐后健康人体生物等效性试验

Bioequivalence of omeprazole enteric coated capsules after high fat meal in healthy volunteers

目的评价中国健康人进食高脂餐后,奥美拉唑肠溶胶囊仿制药与原研药的生物等效性。方法用单中心、随机、开放、两制剂、单次给药、四周期、两序列完全重复交叉试验设计。36例健康受试者被随机分为TRTR组和RTRT组,进食相同高脂餐后,四周期分别单次口服受试制剂(T)或参比制剂(R)20 mg。用液相色谱串联质谱(LC-MS/MS)法测定奥美拉唑肠溶胶囊在人体中的血药浓度,用WinNonLin软件计算主要药代动力学参数。结果 36例健康受试者,口服受试和参比制剂后,血浆中奥美拉唑肠溶胶囊的主要药代动力学参数如下。Cmax分别为(411.77±252.10)和(429.72±275.89)ng·mL^-1;AUC0-t分别为(1556.36±1463.45)和(1751.45±1727.57)ng·h·mL^-1;AUC0-∞分别为(1566.45±1481.16)和(1763.22±1750.07)ng·h·mL^-1;Tmax分别为(4.78±0.92)和(4.95±1.03)h。两种制剂的Cmax、AUC0-t、AUC0-∞的几何均值对应的90%置信区间分别为86.54%~104.73%,86.96%~97.47%和86.95%~96.61%。结论两种制剂在高脂餐后的中国健康受试者中具有生物等效性。

Objective To evaluate the bioequivalence of omeprazole enteric coated capsules and the original drug after eating high-fat meal in Chinese healthy people. Methods A single center, randomized, open, two preparations, single administration, four cycles, two sequence completely repeated crossover design was used. Thirty six healthy subjects were randomly divided into TRTR group and RTRT group. After eating the same high-fat meal, the test preparation(T) or the reference preparation(R) 20 mg were given orally in four cycles. The plasma concentration of omeprazole enteric coated capsules was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS). The main pharmacokinetic parameters were calculated by WinNonlin software. Results The main pharmacokinetic parameters of omeprazole enteric coated capsules in plasma were as follows: Cmax were(411.77±252.10) and(429.72±275.89) ng·mL^-1, AUC0-t were(1556.36±1463.45) and(1751.45±1727.57) ng·h·mL^-1, AUC0-∞ were(1566.45±1481.16) and(1763.22±1750.07) ng·h·mL^-1, Tmax were(4.78±0.92) and(4.95±1.03)h, respectively. The 90% confidence intervals of the geometric mean ratios of Cmax, AUC0-t, AUC0-∞of the two preparations were86. 54%-104. 73%,86. 96%-97. 47% and 86. 95%-96. 61%,respectively. Conclusion The two preparations are bioequivalent in Chinese healthy subjects after high-fat meal.