摘要
目的:开展两种盐酸度洛西汀肠溶胶囊在中国健康人体生物等效性研究.方法:在健康成年受试者中进行单中心、随机、开放、两周期、两序列、交叉、单次给药试验设计,共有 72 例健康受试者随机入组,用液相串联质谱测定人血浆中度洛西汀含量,用Phoenix WinNonlin 8.2 软件评价药代动力学参数,并对测试制剂与参比制剂进行生物等效性评价.结果:两组受试者服用测试制剂和参比制剂后,测试制剂和参比制剂空腹组度洛西汀动力学参数Cmax分别为(26.2±8.04)和(26.9±7.30)ng/ml;AUC0-t分别为(444.07±148.81)和(442.00±156.99)ng·h/ml;AUC0-∞分别为(458.87±156.82)和(460.42±174.83)ng·h/ml,测试制剂和参比制剂餐后组度洛西汀动力学参数Cmax分别为(24.3±8.51)和(24.9±10.2)ng/ml;AUC0-t 分别为(400.59±206.52)和(411.42±229.82)ng·h/ml;AUC0-∞分别为(418.54±225.41)和(429.91±254.89)ng·h/ml.两种制剂Cmax、AUC0-t和AUC0-∞几何均值比及其 90%置信区间均在 80.00%～125.00%.结论:两种盐酸度洛西汀肠溶胶囊在中国健康受试者中具有生物等效性,安全性良好.
Abstract
Objective:To study the bioequivalence of two enteric-coated duloxetine hydrochloride capsules in healthy Chinese subjects.Methods:This was a single-center,randomized,open,two-cycle,two-sequence,crossover,single-dose trial in healthy adult subjects.A total of 72 healthy subjects were randomly enrolled in the study.The content of duloxetine in human plasma was determined by liquid tandem mass spectrometry,and the pharmacokinetic parameters were evaluated using Phoenix WinNonlin 8.2 software.The bioequivalence of the test and reference preparations was also evaluated.Results:After taking test preparation and reference preparation,Cmax of duloxetine in the fasting group of test preparation and reference preparation were(26.2±8.04)and(26.9±7.30)ng/ml,respectively.AUC0-t were(400.59±206.52)and(411.42±229.82)ng·h/ml,respectively.AUC0-∞were(418.54±225.41)and(429.91±254.89)ng·h/ml,respectively.The kinetic parameters Cmax of duloxetine in the test preparation and the reference preparation group were(24.3±8.51)and(24.9±10.2)ng/ml,respectively.AUC0-t were(400.59±206.52)and(411.42±229.82)ng·h/ml,respectively.AUC0-∞were(418.54±225.41)and(429.91±254.89)ng·h/ml,respectively.The geometric mean ratios of Cmax,AUC0-t,AUC0-∞Cmax,and 90%confidence interval of the two formulations ranged from 80.00%to 125.00%.Conclusion:The two kinds of duloxetine hydrochloride enteric-coated capsules have bioequivalence and good safety in healthy Chinese subjects.
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