摘要
目的:研究辛伐他汀片及其活性代谢物辛伐他汀酸在健康人体内的药动学特征和生物等效性评价。方法:24名健康受试者随机交叉、单剂量口服40 mg参比和试验辛伐他汀片后;采用LC-MS/MS测定血浆中辛伐他汀和辛伐他汀酸的浓度;应用DAS2.1.1软件计算药动学参数,并进行生物等效性评价。结果:参比和试验制剂辛伐他汀的主要药动学参数如下:Cmax分别为(6.8±4.0)μg·L-1和(6.9±4.5)μg·L-1;tmax分别为(2.4±1.9)h和(2.2±1.5)h;t1/2分别为(5.0±2.6)h和(6.3±6.7)h;AUC0-24分别为(38.1±27.0)μg·h·L-1和(36.5±24.2)μg·h·L-1;AUC0-∞分别为(40.7±29.3)μg·h·L-1和(41.8±28.7)μg·h·L-1。参比和试验制剂辛伐他汀酸的主要药动学参数如下:Cmax分别为(3.8±1.7)μg·L-1和(3.8±1.6)μg·L-1;tmax分别为(4.3±1.6)h和(4.2±1.0)h;t1/2分别为(5.8±3.2)h和(7.3±6.9)h;AUC0-24分别为(30.1±11.1)μg·h·L-1和(30.0±10.5)μg·h·L-1;AUC0-∞分别为(34.0±14.4)μg·h·L-1和(35.6±17.4)μg·h·L-1。以AUC0-24计算辛伐他汀和辛伐他汀酸的相对生物利用度分别为(105.7±55.6)%和(106.5±42.8)%。结论:经方差分析及双单侧t检验结果显示,辛伐他汀与辛伐他汀酸的试验制剂和参比制剂在人体内生物等效。
OBJECTIVE To investigate the pharmacokinetics and bioequivalence of simvastatin tablets and its metabolite in Chinese healthy subjects.METHODS A single oral dose of 40 mg reference or test simvastatin tablets was given to each healthy volunteer according to an open randomized crossover design.The concentrations of simvastatin and simvastatin acid in plasma were determined by LC-MS/MS method.The pharmacokinetic parameters were calculated and the bioequivalence was evaluated with DAS ver 2.1.1 program.RESULTS The main pharmacokinetic parameters of reference and test simvastatin were as follows： Cmax（6.8±4.0）μg·L-1 and（6.9±4.5）μg·L-1;tmax（2.4±1.9）h and（2.2±1.5）h;t1/2（5.0±2.6）h and（6.3±6.7）h;AUC0-24（38.1±27.0）μg·h·L-1 and（36.5±24.2）μg·h·L-1;AUC0-∞（40.7±29.3）μg·h·L-1 and（41.8±28.7）μg·h·L-1.The main pharmacokinetic parameters of reference and test simvastatin acid were as follows： Cmax（3.8±1.7）μg·L-1 and（3.8±1.6）μg·L-1;tmax（4.3±1.6）h and（4.2±1.0）h;t1/2（5.8±3.2）h and（7.3±6.9）h;AU0-24（30.1±11.1） μg·h·L-1 and（30.0±10.5） μg·h·L-1;AUC0-∞（34.0±14.4） μg·h·L-1 and（35.6±17.4） μg·h·L-1.The relative bioavailability of simvastatin and simvastatin acid was（105.7±55.6）% and（106.5±42.8）%,respectively.CONCLUSION The results showed that the test and reference formulations of simvastatin and simvastatin acid were bioequivalent.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2012年第19期1530-1533,共4页
Chinese Journal of Hospital Pharmacy
