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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 the bioequivalence of ubenimex capsules with Japanese original products after the domestic production process was changed. Methods Twenty-four healthy male subjects were treated with triple-crossover single oral dose of T1 (10 mg / kg) and T2 (30 mg / kg) by ultra performance liquid chromatography-mass spectrometry (UPLC-MS / MS) The concentration of ubenimex in the plasma at different time point after 30 mg R (30mg / granule) was calculated. The pharmacokinetic parameters and bioequivalence were calculated by WinNonlin6.1 software. Results One patient was excluded from taking medication and the remaining 23 subjects had oral administration of T1 and T2 and R 30 mg of crude drug. The peak concentrations of ubenimex in plasma (Cmax) were (2 646.73 ± 454.09 ng / mL, 2 675.91 ± 474.32 ng / mL, and (2 432.79 ± 544.32) ng / mL, respectively. The peak time was (0.68 ± 0.23) h and (0.76 ± 0.19) (0.77 ± 0.26) h; the area under the curve AUC0-t were (3 925.23 ± 478.34) ng · h / mL, 3 804.62 ± 448.84 ng · h / mL and 3 789.30 ± 443.15 respectively ng · h) / mL and AUC0-∞ were (3 938.31 ± 479.54) ng · h / mL · 3 817.26 ± 450.90 ng · h / mL · 3 800.90 ± 444.77 ng · h ) / mL and the drug clearance rate (CL / F) were (7.72 ± 0.92) L / h, (7.97 ± 0.98) L / h and (7.99 ± 0.90) L / h, respectively. The apparent volume of distribution (26.08 ± 9.20) L, (25.65 ± 10.22) L, (26.03 ± 10.05) L, respectively. The relative bioavailability (F0-t) of T1, T2 and R were (103.90 ± 9.19)% and (100.77 ± 9.36)%, respectively. The F0-∞ were (103.93 ± 9.20)% and (100.79 ± 9.33)%, respectively. Conclusion The two kinds of domestic ubiquinone capsules are bioequivalent to the original Japanese products.