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目的:研究氯沙坦钾胶囊及其片剂在健康人体内的药动学特征,并评价两种制剂间的生物等效性。方法:20名健康男性志愿受试者随机交叉单剂量口服试验制剂和参比制剂50 mg,清洗期1周,LC-MS/MS法测定血浆氯沙坦和代谢物氯沙坦羧酸(E-3174)浓度。药代参数的计算与统计分析使用DAS2.0软件。结果:口服试验制剂和参比制剂后,受试者的氯沙坦和E-3174主要药代动力学参数如下:氯沙坦Cmax分别为(183.83±91.30),(176.45±93.97)μg.L-1;AUC0-t分别为(333.18±105.00),(323.75±101.92)μg.h.L-1;AUC0-∞分别为(344.88±104.15),(341.32±106.13)μg.h.L-1;t1/2分别为(1.84±0.52),(1.99±0.60)h;tmax分别为(0.70±0.22),(0.98±0.62)h。E-3174 Cmax分别为(344.85±114.33),(329.95±106.42)μg.L-1;AUC0-t分别为(2 445.09±608.97),(2 332.54±564.72)μg.h.L-1;AUC0-∞分别为(2 503.45±612.62),(2 390.92±567.03)μg.h.L-1;t1/2分别为(4.17±0.49),(4.13±0.66)h;tmax分别为(3.14±0.72),(3.39±0.96)h。试验制剂氯沙坦钾胶囊中氯沙坦和E-3174相对生物利用度分别为(104.9±20.7)%和(105.2±12.1)%。结论:本试验采用的氯沙坦钾胶囊和氯沙坦钾片为生物等效制剂。
OBJECTIVE: To study the pharmacokinetics of losartan potassium capsule and its tablet in healthy volunteers and to evaluate the bioequivalence between the two preparations. Methods: Twenty healthy male volunteers were randomized to receive a crossover single oral dose of 50 mg test preparation and reference preparation for 1 week. LC-MS / MS method was used to determine the plasma levels of losartan and metabolite losartan carboxylic acid (E -3174) concentration. Pharmacokinetic parameters of the calculation and statistical analysis using DAS2.0 software. RESULTS: The main pharmacokinetic parameters of losartan and E-3174 were as follows after oral administration of the test formulation and reference formulation: Losartan Cmax was (183.83 ± 91.30), (176.45 ± 93.97) μg.L -1; AUC0-t were (333.18 ± 105.00) and (323.75 ± 101.92) μg.hL-1; AUC0-∞ were (344.88 ± 104.15) and (1.84 ± 0.52) and (1.99 ± 0.60) h respectively; tmax was (0.70 ± 0.22) and (0.98 ± 0.62) h, respectively. The Cmax of E-3174 were (344.85 ± 114.33) and (329.95 ± 106.42) μg.L-1, respectively. The AUC0-t were (2 445.09 ± 608.97) and (2 332.54 ± 564.72) μg.hL- (3.14 ± 0.72), (3.39 ± 0.67) and (3.39 ± 0.697) μg.hL-1, respectively, and ± 0.96) h. The relative bioavailability of losartan and E-3174 in the losartan potassium capsule was (104.9 ± 20.7)% and (105.2 ± 12.1)%, respectively. Conclusion: The losartan potassium capsules and losartan potassium tablets used in this study are bioequivalent formulations.