头孢地尼颗粒剂在中国健康受试者空腹及餐后的生物等效性研究

Fasting/postprandial bioequivalence of cefdinir granules in healthy Chinese subjects

目的:研究在中国健康成年受试者中空腹及餐后给药条件下单次口服头孢地尼参比制剂和受试制剂的生物等效性。方法:采用单中心、随机、开放、单剂量、两制剂、两周期、双交叉试验设计。空腹及餐后状态下随机交叉服用受试制剂头孢地尼颗粒或参比制剂头孢地尼细粒剂50 mg,采用高效液相色谱-串联质谱法(HPLC-MS/MS)测定血浆中头孢地尼的浓度,运用Phoenix WinNonlin 8.3.4软件非房室模型计算主要药代动力学参数,评价两种制剂的生物等效性。记录受试者发生的不良事件和严重不良事件,评价两种制剂的安全性。结果:空腹入组26例受试者,口服头孢地尼颗粒受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(747.85±205.45)和(740.92±181.86)ng/ml,AUC_(0-t)分别为(3 881.30±1 033.99)和(3 746.00±910.99)h·ng/ml,AUC_(0-∞)分别为(3 908.80±1 047.44)和(3 773.70±922.38)h·ng/ml。餐后入组30例受试者,口服头孢地尼颗粒受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(329.97±55.30)和(328.43±50.81)ng/ml,AUC_(0-t)分别为(1 849.40±292.36)和(1 863.30±289.27)h·ng/ml,AUC_(0-∞)分别为(1 924.80±322.76)和(1 941.30±303.30)h·ng/ml。空腹状态下和餐后状态下单次口服给药后受试制剂与参比制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)几何均值比值的90%置信区间均在80.00%~125.00%。研究过程中共发生26例次不良事件,严重程度均为轻度,未发生严重不良事件。结论:受试制剂头孢地尼颗粒剂和参比制剂头孢地尼细粒剂在空腹和餐后状态下生物等效。

Objective:To investigate the bioequivalence of a single oral cefdinir reference preparation and test preparation in healthy Chinese adults under fasting and postprandial conditions.Method:A single-center,randomized,open,single-dose,two-agent,two-cycle,double-cross experiment was designed.The test preparation cefdinir granules or reference preparation cefdinir fine granules(50 mg) were randomly cross-administered in the fasting/postprandialstate,and the concentration of cefdinir in plasma was determined by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).To evaluate the bioequivalence of the two formulations,the main pharmacokinetic parameters were calculated using a non-atrioventricular model using Phoenix WinNonlin 8.3.4 software.Adverse events and serious adverse events were recordedand the safety of the two formulations was evaluated.Results:Twenty-six subjects were enrolled under fasting conditions.The main pharmacokinetic parameters of the test preparation and the reference preparation of oral cefdinir granules were as follows:C_(max)were(747.85 ±205.45) and(740.92 ±181.86) ng/ml;AUC_(0-t)were(3 881.30 ±1 033.99) and(3 746.00±910.99)h·ng/ml;AUC_(0-∞)were(3 908.80±1 047.44)and(3 773.70±922.38)h·ng/ml,respectively.Thirty subjects were enrolled under fed condition.The main pharmacokinetic parameters of the test preparation and the reference preparation of oral cefdinir granules were as follows:C_(max)were(329.97±55.30)and(328.43±50.81) ng/ml;AUC_(0-t)were(1 849.40±292.36)and(1 863.30±289.27) h·ng/ml;AUC_(0-∞)were(1 924.80±322.76)and(1 941.30±303.30) h·ng/ml,respectively.The 90% confidence intervals of C_(max),AUC_(0-t),and AUC_(0-∞)geometric mean ratio between the test preparation and reference preparation in fasting and fed conditions were 80.00%~125%.During the research process,a total of 26 adverse events occurred,all of which were mild in severity,and no serious adverse events occurred.Conclusions:The test preparation of cefdinir granules and the reference preparation of cefdinir fine granules are bioequivalent in fasting and postprandial conditions.