马来酸依那普利片的人体生物等效性研究

 目的用HPLC-MS测定健康受试者口服马来酸依那普利制剂后的血药浓度,估算受试制剂和参比制剂的药动学参数,评价两种制剂的生物等效性和相对生物利用度。方法采用随机二交叉设计试验,20例男性健康志愿受试者,单剂量口服受试制剂和参比制剂的马来酸依那普利片。以高效液相色谱-串联质谱法测定血浆中依那普利和依那普利拉的浓度。采用SPSS及BAPP2.2软件处理计算主要药动学参数。结果受试制剂和参比制剂血浆中马来酸依那普利的t_1/2分别为(1.33±0.22)和(1.25±0.37)h;ρ_max分别为(238.59±55.40)和(230.61±78.29)μg·L^-1,t_max分别为(0.70±0.20)和(0.80±0.20)h,AUC_0-8h分别为(339.03±70.66)和(373.23±108.83)μg·h·L^-1,AUC_0-∞分别为(343.51±71.15)和(378.36±107.35)μg·h·L^-1。依那普利拉的t_1/2分别为(6.26±0.63)和(5.72±0.54)h;ρ_max分别为(83.75±25.91)和(99.13±29.61)μg.L^-1,t_max分别为(3.80±0.60)和(3.40±0.70)h,AUC_{0-36 h}分别为(812.02±181.88)和(803.35±199.50)μg·h·L^-1,AUC_0-∞分别为(832.99±180.85)和(817.36±201.78)μg·h·L^-1,以依那普利和依那普利拉计算的人体相对生物利用度分别为(90.84±39.6)%和(102.8±31.3)%。结论两种制剂在健康人体内具有生物等效性。

Study on Bioequivalenee of Enalapril Maleate Tablet in Chinese Healthy Volunteers

OBJECTIVE To evaluate the bioequivalence of enalapril maleate tablet of tested preparation and reference preparation in healthy volunteers.METHODS A single oral dose of two preparations was given to 20 healthy male volunteers according to a randomized crossover design.Plasma drug concentrations were detected by LC-MS/MS.RESULTS The pharmacokinetic parameters of enalapril maleate of two preparations were as follows:t_1/2(1.33±0.22)and(1.25±0.37)h;ρ_max(238.59±55.40)and(230.61±78.29)μg·L^-1;t_max(0.70±0.20)and(0.80±0.20)h;AUC_{0-8 h}(339.03±70.66)and(373.23±108.83)μg·h·L^-1;AUC_0-∞(343.51±71.15)and(378.36±107.35)μg·h·L^-1,respectively.The pharmacokinetic parameters of enalaprilat were as follows:t_1/2(6.26±0.63)and(5.72±0.54)h;ρ_max(83.75±25.91)and(99.13±29.61)μg·L^-1;t_max(3.80±0.60)and(3.40±0.70)h;AUC_{0-36 h}(812.02± 181.88)and(803.35±199.50)μg·h·L^-1;AUC_0-∞(832.99±180.85)and(817.36±201.78)μg·h·L^-1,respectively.The relative bioavailability of enalapril maleate and enalaprilat were(90.84±39.6)% and(102.8±31.3)%,respectively.CONCLUSION The two formulations are bioequivalent in human body.