头孢拉定胶囊在中国健康受试者的生物等效性研究

Bioequivalence of cefradine capsules in Chinese healthy volunteers

目的评估头孢拉定胶囊在中国健康人体内的生物等效性。方法采用随机开放双交叉试验设计,在空腹和餐后状态下各入组30例健康志愿者,每周期单剂量口服头孢拉定胶囊0.25 g。以液相色谱-串联质谱(LC-MS/MS)法测定血浆中头孢拉定的浓度。用WinNonlin软件计算药动学参数,并进行生物等效性评价。结果空腹状态下,受试制剂与参比制剂的C_(max)分别为11156.33 ng/ml和11747.33 ng/ml,AUC_(0-t)分别为17804.82 ng/(h·ml)和16902.73 ng/(h·ml),AUC_(0-∞)分别为和17879.61 ng/(h·ml)和16984.14 ng/(h·ml);餐后状态下,受试制剂与参比制剂的C_(max)分别为5106.33 ng/ml和5393.67 ng/ml,AUC_(0-t)分别为16729.83 ng/(h·ml)和16010.45 ng/(h·ml),AUC_(0-∞)分别为17168.00 ng/(h·ml)和16241.07 ng/(h·ml)。受试制剂与参比制剂的几何均值比AUC_(0-t)、AUC_(0-∞)、C_(max)的90%可信区间均在80.00%~125.00%之内。结论空腹和餐后条件下,国产头孢拉定胶囊与参比制剂具有生物等效性。

Objective To investigate the bioequivalence of two cefradine capsules in Chinese healthy subjects.Methods This is an open,randomized and two-way crossover clinical trial.In each period,30 healthy subjects received a single dose of either the test or reference cefradine capsule(0.25 g)under fasted and fed conditions.The concentration of cefradine in plasma was determined by liquid chromatoc-tandem mass spectrometry(LC-MS/MS).Pharmacokinetic parameters were calculated with WinNonlin software.Results In the fasting study,the C_(max),AUC_(0-t)and AUC_(0-∞)of test and reference preparation were 11156.33 and 11747.33 ng/ml,17804.82 and 16902.73 ng/(h·ml),17879.61 and 16984.1 ng/(h·ml),respectively.In the fed study,the C_(max),AUC_(0-t)and AUC_(0-∞)of test and reference preparation were 5106.33 and 5393.67 ng/ml,16729.83 and 16010.45 ng/(h·ml),17168.00 and 16241.07 ng/(h·ml),respectively.The 90%confidence intervals of the C_(max),AUC_(0-t)and AUC_(0-∞)for the test and reference preparations were within the range of 80.00%~125.00%.Conclusion The test cefradine capsules and the reference formulation are bioequivalent under both fasting and fed conditions.