【摘要】 目的建立血浆中盐酸西布曲明浓度的检测方法,评价2种盐酸西布曲明口腔崩解片和盐酸西布曲明胶囊的生物等效性。方法采用LC-MS联用技术检测beagle犬血浆中盐酸西布曲明的浓度。根据血药浓度经时数据使用3P97药动学程序拟合求出6条♂性beagle犬单次给药10 mg试验品(盐酸西布曲明口腔崩解片)和10 mg参比品(盐酸西布曲明胶囊)后的体内药动学参数,研究其药动学特征。结果试验品与参比品的体内过程均符合具有一级吸收的二室药动学模型。试验品和参比品单次给药后的主要药动学参数ρmaxt、max和AUC0→t经交叉试验方差分析,差异均具有统计学意义(P<0.05)。试验品和参比品的ρmax、tmax和AUC0→t经对数转换后的双单侧t检验示:两者不具有生物等效性。试验品的相对生物利用度为(279.51±55.01)%。结论本方法能准确、快速、高效地测定beagle犬血浆中的盐酸西布曲明浓度。试验品给药后能够迅速吸收,符合设计制剂特征。更多还原

【Abstract】 AIM To determine the plasma concentration following a single oral dose of sibutramine and evaluate the bioequivalence of sibutramine mouth-dissolving tablets in beagle dogs.METHODS Six male beagle dogs were given sibutramine hydrochloride preparations at the dose level of 10 mg（fast disintegrating tablet as test and sibutramine hydrochloride capsule as reference）.Plasma concentration of sibutramine hydrochloride was assayed by LC-MS.Pharmacokinetic parameters were calculated by official 3P87 program after administration of both preparations.RESULTS The curves of concentration-time of two preparations were both fitted to two compartment model with first order absorption.ρ_max,t_max and AUC_0→t were significantly different between 2 groups（P<0.05）.The two-one side t-test of ρ_max,t_max and AUC_0→t between test and reference preparations after logarithm transition showed that two preparations were not bioequivalence.The relative bioavailability was（279.51±55.01）%.CONCLUSION The drug concentration in beagle dog plasma can be detected efficiently by the LC-MS method.The test tablet can be quickly absorbed and take effect after administration than that of reference.It shows to the characteristics of preparation.更多还原