克拉霉素片在中国健康受试者体内的生物等效性研究

Bioequivalence of clarithromycin tablets in Chinese healthy subjects

目的评价2种克拉霉素片在中国健康受试者的生物等效性和安全性。方法采用随机、开放、单剂量、双周期交叉设计,健康受试者空腹或餐后,单剂量口服克拉霉素片受试制剂与参比制剂,用验证的LC-MS/MS法测定健康受试者给药前后血浆中克拉霉素的药物浓度,用WinNonlin8.0软件对药物检测数据进行药动学参数的计算。结果单次空腹给药受试药物与参比药物克拉霉素的主要药代动力学参数:Cmax分别为(1046.96±625.29),(1003.61±391.25)ng·mL-1;tmax分别为(1.65±1.06),(1.85±1.32)h;t1/2分别为(4.47±1.24),(4.46±0.85)h;AUC0-t分别为(6814.66±3226.85),(6737.63±2272.51)ng·h·mL-1,AUC0-∞分别为(7019.06±3300.30),(6911.08±2336.72)ng·h·mL-1。单次餐后给药受试药物与参比药物克拉霉素的主要药代动力学参数:Cmax分别为(1591.79±655.32),(1734.68±774.47)ng·mL-1;tmax分别为(2.10±0.80),(2.29±0.83)h;t1/2分别为(4.30±1.01),(4.33±0.81)h;AUC0-t分别为(7508.51±2695.74),(7967.50±3618.10)ng·h·mL-1,AUC0-∞分别为(7662.79±2778.69),(8137.65±3763.83)ng·h·mL-1。两药物的主要药代动力学参数Cmax、AUC0-t和AUC0-∞经对数转换后进行方差分析;其90%置信区间空腹状态下分别为89.61%~112.07%,89.10%~107.07%,89.52%~107.22%;餐后状态下分别为82.23%~104.43%,86.74%~106.26%,86.75%~106.23%。结论空腹和餐后状态下,两种克拉霉素片的主要药代动力学参数相近,在中国健康受试者体内具有生物等效性。

Objective To evaluate the bioequivalence and safety of the two clarithromycin tablets in Chinese healthy subjects.Methods An randomized open single-dose two periods crossover design was carried out.Subjects were administered a single oral dose of test and reference clarithromycin tablets fasted or with food.The concentrations of clarithromycin in plasma were determined by LC/MS/MS method.The pharmacokinetic parameters were calculated by WinNonlin 8.0 program.Results The main pharmacokinetic parameters of the tested and reference preparations were as follows:the fasting condition Cmax were(1046.96±625.29),(1003.61±391.25)ng·mL-1;tmax were(1.65±1.06),(1.85±1.32)h;t1/2 were(4.47±1.24),(4.46±0.85)h;AUC0-t were(6814.66±3226.85),(6737.63±2272.51)ng·h·mL-1;AUC0-∞were(7019.06±3300.30)(6911.08±2336.72)ng·h·mL-1.The fed condition Cmaxwere(1591.79±655.32),(1734.68±774.47)ng·mL-1;tmaxwere(2.10±0.80),(2.29±0.83)h;t1/2 were(4.30±1.01),(4.33±0.81)h;AUC0-twere(7508.51±2695.74),(7967.50±3618.10)ng·h·mL-1;AUC0-∞were(7662.79±2778.69),(8137.65±3763.83)ng·h·mL-1.The 90%confidence interval of Cmax,AUC0-tand AUC0-∞of test preparation in fasting condition were 89.61%-112.07%,89.10%-107.07%,89.52%-107.22%;in fed condition were82.23%-104.43%,86.74%-106.26%,86.75%-106.23%.Conclusion The exposures were equivalent between two clarithromycin tablets administered with food or fasted in Chinese healthy subjects.