摘要
目的:研究阿莫西林胶囊在中国健康人体内的生物等效性.方法:以单中心、开放式、随机、双制剂、两周期、两序列交叉试验设计,共48例受试者(空腹试验和餐后试验各24例),口服0.25 g阿莫西林胶囊受试制剂或参比制剂.高效液相色谱—串联质谱(LC-MS/MS)分析方法测定给药后不同时间阿莫西林的血药浓度,并计算主要药代动力学参数,判定两制剂是否等效.结果:空腹试验显示,受试制剂和参比制剂阿莫西林的药物峰浓度(Cmax)分别为(5 483.296±1 321.102)ng/mL、(5 611.291±1 659.407)ng/mL,从时间0到t之间血药浓度—时间曲线下面积(AUC0-t)分别为(13 255.3±1 715.7)h·ng/mL、(13 115.5±2 091.7)h·ng/mL,从0时到无限时间(∞)的血药浓度—时间曲线下面积(AUC0-∞)分别为(13 329.4±1 718.8)h·ng/mL、(13 192.7±2 107.1)h·ng/mL,达峰时间(Tmax)均为1.38 h.餐后试验显示,受试制剂和参比制剂阿莫西林的Cmax分别为(4 218.072±780.598)ng/mL、(4 156.713±877.752)ng/mL,AUC0-t分别为(13 073.9±1 584.3)h·ng/mL、(12 817.8±1 575.5)h·ng/mL,AUC0-∞分别为(13 166.8±1 606.0)h·ng/mL、(12 914.8±1 587.2)h·ng/mL,Tmax均为3.00 h.两种试验制剂Cmax、AUC0-t、AUC0-∞几何均值比值的90%置信区间(CI)均在可接受的生物等效性范围内(80%～125%).结论:两种阿莫西林胶囊在中国健康志愿者体内吸收速度和吸收程度生物等效.
Abstract
Objective:To study the bioequivalence of amoxicillin capsules in healthy Chinese subjects.Meth-ods:A single-center,open-label,randomized,two-formulation,two-period,two-sequence crossover trial was de-signed.A total of 48 subjects(24 in each fasting and postprandial trial)were orally administered 0.25 g of amoxi-cillin capsule test formulation or reference formulation.High performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was used to determine the plasma concentration of amoxicillin at different times after administration,and the main pharmacokinetic parameters were calculated to determine whether the two formulations were equivalent.Results:The fasting trial showed the maximum plasma concentration(Cmax)of the test formulation and the reference formulation of amoxicillin were(5,483.296±1,321.102)ng/mL and(5,611.291±1,659.407)ng/mL,respectively;the area under the concentration-time curve from time 0 to time t(AUC0-t)were(13,255.3±1,715.7)h·ng/mL and(13,115.5±2,091.7)h·ng/mL,respectively;the AUC from time 0 to infinity(AUC0-∞)were(13,329.4±1,718.8)h·ng/mL and(13,192.7±2,107.1)h·ng/mL,respectively;both of their Tmax was 1.38 h.The postprandial trial showed the Cmax of the test formulation and the reference formulation of amoxicillin were Cmax were(4,218.072±780.598)ng/mL and(4,156.713±877.752)ng/mL,respectively;AUC0-t were(13,073.9±1,584.3)h·ng/mL and(12,817.8±1,575.5)h·ng/mL,respectively;AUC0-∞were(13,166.8±1,606.0)h·ng/mL and(12914.8±1587.2)h·ng/mL,respectively;both of their Tmax was 3.00 h.The 90%confi-dence intervals(CI)of the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ of the two preparations were all within the acceptable bioequivalence range(80%-125%).Conclusion:The absorption rate and degree of two amoxicillin capsules are bioequivalent in Chinese healthy subjects.
基金项目
湖南省自然科学基金资助项目(2022JJ80100)
复杂基质样本生物分析湖南省重点实验室(2017TP1037)
湖南省复杂基质样本生物分析国际科技创新合作基地(2019CB1014)
湖南省科技人才托举工程(2023TJN20)
维普
万方数据