摘要
目的评价国产变更生产工艺后两种规格的乌苯美司胶囊与日本原研产品的生物等效性。方法采用超高效液相色谱-质谱联用法(UPLC-MS/MS法)测定24例健康男性受试者三交叉单剂口服两种试验制剂T1(10mg/粒)、T2(30mg/粒)和原研产品R(30mg/粒)30mg后不同时点血浆中乌苯美司浓度,利用WinNonlin6.1软件进行药代动力学参数计算和生物等效性评价。结果 1例受试者因未依从方案服药而被剔除,余下23例受试者口服试验制剂T1、T2和原研产品R 30mg后,血浆中乌苯美司的峰浓度(Cmax)分别为(2 646.73±454.09)ng/mL、(2 675.91±474.32)ng/mL、(2 432.79±544.32)ng/mL;达峰时间(Tmax)分别为(0.68±0.23)h、(0.76±0.19)h、(0.77±0.26)h;曲线下面积AUC0-t分别为(3 925.23±478.34)(ng·h)/mL、(3 804.62±448.84)(ng·h)/mL、(3 789.30±443.15)(ng·h)/mL;AUC0-∞分别为(3 938.31±479.54)(ng·h)/mL、(3 817.26±450.90)(ng·h)/mL、(3 800.90±444.77)(ng·h)/mL,药物清除率(CL/F)分别为(7.72±0.92)L/h、(7.97±0.98)L/h、(7.99±0.90)L/h,表观分布容积(Vd)分别为(26.08±9.20)L、(25.65±10.22)L、(26.03±10.05)L。T1、T2与R的相对生物利用度F0-t分别为(103.90±9.19)%、(100.77±9.36)%,F0-∞分别为(103.93±9.20)%、(100.79±9.33)%。结论两种规格的国产乌苯美司胶囊均与日本原研产品具有生物等效性。
Objective To evaluate bioequivalence of two specifications of ubenimex capsules in comparison with the Japanese branded product（R）.Methods The study adopted a 3-way crossover design in twenty-four healthy male volunteers,whose plasma concentrations of ubenimex were determined by UPLC-MS/MS after administration a single oral dose of 30 mg of domestic ubenimex T1（10 mg/capsule）,T2（30 mg/capsule）and branded ubenimex R（30mg/capsule）sequentially.The bioequivalence was evaluated using WinNonlin6.1statistical analysis software.Results One volunteer was excluded because of failure to follow medication instructions.The main pharmacokinetic parameters of ubenimex of T1,T2 and R were as follows：Cmax（2 646.73±454.09）ng/mL,（2 675.91±474.32）ng/mL and（2 432.79±544.32）ng/mL,respectively;Tmax（0.68±0.23）h,（0.76±0.19）h and（0.77±0.26）h,respectively;AUC0-t（3 925.23±478.34）（ng·h）/mL,（3 804.62±448.84）（ng·h）/mL and（3 789.30±443.15）（ng·h）/mL,respectively;AUC0-∞（3 938.31±479.54）（ng·h）/mL,（3 817.26±450.90）（ng·h）/mL and（3 800.90±444.77）（ng·h）/mL,respectively;CL/F（7.72±0.92）L/h,（7.97±0.98）L/h and（7.99±0.90）L/h,respectively;Vd（26.08±9.20）L,（25.65±10.22）L and（26.03±10.05）L,respectively.The relative bioavailability F0-tand F0-∞ of T1 and T2against the branded preparation R were（103.90±9.19）% and（100.77±9.36）%,and（103.93±9.20）% and（100.79±9.33）%,respectively.Conclusion Both ubenimex capsules T1 and T2are bioequivalent to the Japanese branded products.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2016年第1期85-89,92,共6页
Journal of Sichuan University(Medical Sciences)
