Bioequivalence of Benazepril Hydrochloride Tablet and Its Active Metabolites in Healthy Chinese Subjects
Objective To evaluate the bioequivalence of test and reference preparations after single oral administration of benazepril hydrochloride tablets in healthy subjects under fasting and postprandial conditions.Methods The volunteers were assigned to either T-R(test preparation-reference preparation)or R-T(reference preparation-test preparation)sequence by 1·1 ratio.Sin-gle-center,randomized,open,two-cycle,double-sequence,self-crossover,fasting and postprandial single administration protocols were used for experiment design.The plasma concentrations of benazepril hydrochloride were determined by high performance liquid chromatography-tandem mass spectrometry.The main pharmacokinetic parameters Cmax,AUC0-t and AUC0-∞ were ana-lyzed using the non-atrioventricular mode of WinNonlin.Tmax was analyzed by nonparametric rank sum test.Results The Cmax,AUC0-t,AUC0-∞and Tmax of benazepril test and reference prepara-tions in the fasting group were(207.86±70.77)ng·mL-1 and(205.20±70.37)ng·mL-1,(168.91±36.03)h×ng·mL-1 and(170.23±38.37)h×ng·mL-1,(171.01±36.15)h×ng·mL-1 and(172.27±38.49)h×ng·mL-1,and(0.48±0.11)h and(0.49±0.17)h,respectively.The Cmax,AUC0-t,AUC0-∞ and Tmax of test and reference preparations of active metabolite benazepril-atin the fasting group were(270.45±69.07)ng·mL-1 and(271.86±65.90)ng·mL-1,(1 490.10±295.32)h×ng·mL-1 and(1 487.96±285.39)h×ng·mL-1,(1 535.19±289.52)h×ng·mL-1 and(1 532.63±285.26)h×ng·mL-1,and(1.45±0.47)h and(1.41±0.33)h,respec-tively.The Cmax,AUC0-t,AUC0-∞ and Tmax of benazepril test and reference preparations in the postprandial group were(102.05±41.17)ng·mL-1and(112.04±49.39)ng·mL-1,(149.19±32.76)h×ng·mL-1 and(151.70±33.78)h×ng·mL-1,(151.02±33.08)h×ng·mL-1 and(154.03±33.99)h×ng·mL-1,and(1.14±0.65)h and(1.09±0.60)h,respectively.The Cmax,AUC0-t,AUC0-∞ and Tmax of benazeprilat test and reference preparations in the postprandial group were(207.71±50.76)ng·mL-1 and(211.68±66.50)ng·mL-1,(1 366.01±292.24)h×ng·mL-1 and(1 343.78±315.41)h×ng·mL-1,(1 414.95±297.71)h×ng·mL-1 and(1 387.03±314.17)h×ng·mL-1,and(2.46±0.87)h and(2.46±0.85)h,respectively.The 90%confidence intervals of the ratio of geometric means of Cmax,AUC0-t and AUC0-∞ of benazepril and benaze-prilat fell within the 80%-125%range.The Tmax was not significantly different between the two preparations(P＞0.05).Conclusion The test and reference preparations of benazepril hydrochlo-ride tablets are bioequivalent.
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