氯沙坦钾片在健康人体的生物等效性

目的评价2种氯沙坦钾片(血管紧张素Ⅱ受体拮抗药)在健康人体的生物等效性。方法用双交叉设计,24名健康男性志愿者随机分为2组,单剂量口服氯沙坦钾片试验药物或对照药物50 mg,用液相色谱-串联质谱法同时测定血浆中氯沙坦及其活性代谢产物E3174的血药浓度,用BAPP 2.0软件计算药代动力学参数和生物利用度。结果氯沙坦:试验药物与对照药物的Cmax分别为(253.10±155.43),(232.37±136.66)ng.mL-1;Tmax分别为(1.09±0.70),(1.30±0.80)h;t1/2分别为(1.93±0.32),(1.98±0.53)h;AUC0-12分别为(454.19±166.61),(414.97±152.22)ng.h.mL-1,可信区间99.4%～118.6%;试验药物对于对照药物的平均相对生物利用度F为(112.0±29.9)%。E3174:试验药物与对照药物的Cmax分别为(447.45±132.66),(430.81±135.78)ng.mL-1;Tmax分别为(3.56±1.14),(3.77±1.14)h;t1/2分别为(4.55±0.61),(4.67±0.68)h;AUC0-36分别为(3522.17±1162.22),(3307.16±1078.13)ng.h.mL-1,可信区间100.5%～111.8%。试验药物对于对照药物的平均相对生物利用度F为(107.2±16.8)%。结论 2种氯沙坦钾药物具有生物等效性。

Bioequivalence of losartan potassium tablets in Chinese healthy volunteers

Objective To evaluate the bioequivalence of the two losartan potassium tablets(angiotensin Ⅱ receptor) in Chinese healthy volunteers.Methods A single oral dose 50 mg of tested and referened losartan potassium tablets were given to 24 volunteers according to an open randomized crossover design.The concentrations of losartan and its active metabolite E3174 in plasma were determined by LC-MS/MS simultaneously.The pharmacokinetic parameters were caculated and the bioequivalence was compared by BAPP 2.0 program.Results The main pharmacokinetic parameters of losartan of the test and reference preparations were as follows: Cmax were(253.10±155.43),(232.37±136.66) ng·mL-1;Tmax were(1.09±0.70),(1.30±0.80) h;t1/2 were(1.93±0.32),(1.98±0.53) h;AUC0-12 were(454.19±166.61),(414.97±152.22) ng·h·mL-1,the confidence interval 99.4%-118.6%.The relative bioavailability of losartan of test preparations was(112.0±29.9)%.The main pharmacokinetic parameters of E3174 of the test and reference preparations were as follows:Cmax were(447.45±132.66),(430.81±135.78) ng·mL-1;Tmax were(3.56±1.14),(3.77±1.14) h;t1/2 were(4.55±0.61),(4.67±0.68) h;AUC0-36 were(3522.17±11162.22),(3307.16±1078.13) ng·h·mL-1,the confidence interval was 100.5%-111.8%.The relative bioavailability of E3174 of test preparations was(107.2±16.8)%.The main pharmacokinetic parameters of losartan and E3174 showed no statistically significant difference between two preparations.Conclusion The two preparations were bioequivalent.