头孢氨苄胶囊在中国健康受试者的药动学及生物等效性研究

Pharmacokinetic and Bioequivalence of Cefalexin Capsules in China Healthy Subjects

目的:评价2种头孢氨苄胶囊在中国健康受试者的生物等效性及安全性。方法:按单中心、开放、随机、单次给药、两制剂、两序列、两周期、交叉试验设计。空腹和餐后条件下各入组24例受试者,随机交叉单次口服受试制剂和参比制剂250 mg,用LC-MS/MS法测定血浆中头孢氨苄的浓度,用WinNonlin 6.3软件计算头孢氨苄的药动学参数,并进行生物等效性评价。结果:受试者服用受试制剂和参比制剂后,空腹组血浆中头孢氨苄的主要药代动力学参数如下:C max分别为(10600±1930),(9950±2090)ng·L^-1;AUC 0-t分别为(17100±2470),(16600±2600)ng·L^-1·h;AUC 0-∞分别为(17300±2570),(16700±2680)ng·L^-1·h;餐后组血浆中头孢氨苄的主要药代动力学如下:C max分别为(6220±1470),(6040±1370)ng·L^-1;AUC 0-t分别为(16900±2740),(16500±2450)ng·L^-1·h;AUC 0-∞分别为(17100±2820),(16700±2520)ng·L^-1·h。2种制剂的C max、AUC 0-t和AUC 0-∞,经对数转换后90%置信区间分别为空腹状态下98.47%~116.50%,101.02%~105.57%,101.09%~105.63%;餐后状态下93.19%~112.83%,100.43%~103.63%,100.83%~103.76%。结论:2种头孢氨苄胶囊在中国健康受试者中具有生物等效性。

Objective:To evaluate the bioequivalence of two kinds of cefalexin capsules in China healthy subjects.Methods:This was a single-center′randomized′open-label′single-dose′two-period′cross-over pharmacokinetic study.A total of 24 subjects in fasted and 24 subjects in a fed state were given single oral dose of test and reference preparation of cefalexin capsule(each 250mg),respectively.The concentration of cefalexin in human plasma was measured by LC-MS/MS.Main pharmacokinetic parameters were calculated by using WinNonlin 6.3 software.Results:The main pharmacokinetic parameters of cefalexin of the test and the reference preparations were as follows:the fasting state C max were(10600±1930),(9950±2090)ng·L^-1.AUC 0-t were(17100±2470),(16600±2600)ng·L^-1·h.AUC 0-∞were(17300±2570),(16700±2680)ng·L^-1·h.The fed state were(6220±1470),(6040±1370)ng·L^-1.AUC 0-t were(16900±2740),(16500±2450)ng·L^-1·h.AUC 0-∞were(17100±2820),(16700±2520)ng·L^-1·h.The 90%confidential interval of C max、AUC 0-t and AUC 0-∞of tested formulation in the fasting state were 98.47%-116.50%,101.02%-105.57%,101.09%-105.63%.The fed state were 93.19%-112.83%,100.43%-103.63%,100.83%-103.76%.Conclusion:Two kinds of cefalexin capsules are determined to be bioequivalent.