盐酸克林霉素胶囊随机开放两周期两交叉的人体生物等效性试验

A randomized,open-label,double-cycle,double-crossover bioequivalence trial of clindamycin hydrochloride capsules in healthy human subjects

目的研究健康人群在空腹和餐后单剂量口服盐酸克林霉素胶囊受试制剂和参比制剂是否具有生物等效性(BE)。方法采用随机、开放、单剂量、单中心、自身交叉设计,液相色谱串联质谱(LC-MS/MS)法测定健康受试者空腹(n=24)或餐后(n=24)给药后血浆中克林霉素的药物浓度,使用Phoenix WinNonlin软件(Certara USA Inc,7.0)计算药动学参数,使用SAS 9.2软件进行生物等效性评价。结果空腹生物等效性(BE)试验:24名健康受试者分别单次空腹服用克林霉素受试制剂和参比制剂0.15 g后,Cmax、AUC0-t及AUC0-∞的几何均值的比值分别为92.29%,95.32%和95.59%,90%CI分别为84.12%~101.27%,90.14%~100.79%和90.49%~100.98%,均落在等效区间80.00%~125.00%;餐后生物等效性(BE)试验:24名健康受试者分别高脂餐后服用受试制剂和参比制剂0.15 g后,Cmax、AUC0-t及AUC0-∞的几何均值的比值分别为95.79%,100.92%和101.65%,90%CI分别为87.75%~104.56%,93.48%~108.95%和94.09%~109.81%,均落在等效区间80.00%~125.00%。结论两制剂在空腹和餐后条件下,具有生物等效性。

Objective To evaluate the bioequivalence(BE)of a single dose of clindamycin hydrochloride capsule under fasting and fed conditions versus reference preparation in healthy subjects.Methods It was a randomized,open-label,double-cycle,double-crossover trial.Plasma concentration of clindamycin hydrochloride under fasting(n=24)and fed conditions(n=24)in healthy subjects was measured by liquid chromatography with tandem mass spectrometry(LC-MS/MS).Phoenix WinNonlin 7.0 and SAS 9.2 software were used to the measurement of pharmacokinetics(PK)parameters and bioequivalence analysis,respectively.Results The maximum concentration(Cmax),the area under the concentration-time curve from dosing to time t(AUC0-t)and the area under the concentration-time curve from dosing to infinity(AUC0-∞)in 24 healthy subjects medicated with a single dose of clindamycin hydrochloride capsule(0.15g)and the reference preparation 0.15g under fasting condition were 92.29%(90%CI 84.12%-101.27%),95.32%(90%CI 90.14%-100.79%)and 95.59%(90%CI 90.49%-100.98%),respectively,which were all in the range of equivalent interval of 80.00%-125.00%.The Cmax,AUC0-t and AUC0-∞in 24 healthy subjects medicated with a single dose of clindamycin hydrochloride capsule(0.15 g)and the reference preparation 0.15g under high-fat fed condition were 95.79%(90%CI 87.75%-104.56%),100.92%(90%CI 93.48%-108.95%)and 101.65%(90%CI 94.09%-109.81%),respectively,which were all in the range of equivalent interval of 80.00%-125.00%.Conclusion The two formulations are bioequivalent to healthy adult volunteers under fasting and fed conditions.