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目的评价国产氯沙坦钾片在健康人体的生物等效性。方法纳入20例中国健康成年男性志愿者,随机分为两组,按自身前后对比双周期交叉给药,晨起空腹口服试验制剂或参比制剂50 mg。使用HPLC-MS/MS法检测单次空腹口服试验制剂与参比制剂后血浆中氯沙坦及其活性代谢产物E-3174的浓度。药代参数的计算与处理及生物等效性评价使用DAS 2.1.1统计分析软件。结果试验制剂与参比制剂中,原型药物的ρmax分别为(207.50±68.14),(187.23±89.92)μg.L-1;tmax分别为(1.69±1.70),(1.53±0.76)h;AUC0-12 h分别为(457.79±126.46),(442.08±137.48)μg.h.L-1;t1/2分别为(2.09±0.59),(2.01±0.33)h。代谢产物E-3174的ρmax分别为(642.05±280.08),(659.91±295.72)μg.L-1;tmax分别为(4.10±1.86),(4.23±1.69)h;AUC0-12 h分别为(4 702.39±1 803.18),(4 703.28±1 959.33)μg.h.L-1;t1/2为(4.82±0.84),(5.13±1.94)h。结论试验制剂和参比制剂中相应的原型药物和E-3174的主要药代参数差异无统计学意义,试验制剂与参比制剂生物等效。
Objective To evaluate the bioequivalence of domestic losartan potassium tablets in healthy volunteers. Methods Twenty healthy male Chinese volunteers were enrolled and divided into two groups at random. The patients were given double-period cross-over before and after treatment, and 50 mg of the test preparation or reference preparation was taken in the morning. The concentrations of losartan and its active metabolite E-3174 in plasma after a single fasting oral test and reference formulation were determined by HPLC-MS / MS. Calculation and processing of pharmacokinetic parameters and bioequivalence assessment using DAS 2.1.1 statistical analysis software. Results The pmax of the prototype drug in the test and reference preparations were (207.50 ± 68.14) and (187.23 ± 89.92) μg.L-1, respectively; the tmax were 1.69 ± 1.70 and 1.53 ± 0.76 h, (457.79 ± 126.46), (442.08 ± 137.48) μg.hL-1 at 12 h, and (2.09 ± 0.59) and (2.01 ± 0.33) h at t1 / 2, respectively. The pmax of the metabolite E-3174 was (642.05 ± 280.08) and (659.91 ± 295.72) μg.L-1, respectively; the tmax was 4.10 ± 1.86 and 4.23 ± 1.69 h, respectively 702.39 ± 1 803.18), (4 703.28 ± 1 959.33) μg.hL-1; t1 / 2 was (4.82 ± 0.84) and (5.13 ± 1.94) h, respectively. Conclusion The main pharmacokinetic parameters of the corresponding prototype drugs and E-3174 in the test and reference preparations were not statistically different. The test preparations and the reference preparations were bioequivalent.