国产辛伐他汀片与原研制剂的生物等效性研究

目的：考察国产辛伐他汀片与原研制剂的的人体生物利用度,评价两制剂在健康人体的生物等效性.方法：18名健康成年男性志愿者采用随机自身交叉对照试验设计,单剂量口服辛伐他汀片40 mg,用LC-MS/MS法测定血浆中辛伐他汀浓度,采用DAS 3.2.2程序拟合药动学参数,并进行生物等效性评价.结果：单剂量口服40 mg辛伐他汀试验制剂（国产）和参比制剂后,两药的主要药动学参数分别为tmax（4.54±5.35）和（2.32±1.72） h;Cmax：（5.63±4.03）和（7.29±3.84） ng·ml-1;t1/2：（6.31±4.99）和（4.67±3.07） h;AUC（0-t）：（38.75 ±29.55）和（35.54±30.12）ng·h·ml-1;AUC（∞）：（67.31±60.25）和（40.36±34.78）ng·h·ml-1.试验制剂与参比制剂比较,相对生物利用度为117.2％.受试制剂的AUC0→t 90％可信限为89.5％～ 153.5％,AUC0→ 90％可信限为118.1％～198.7％,落在参比制剂对应参数80％ ～ 125％范围外.结论：两制剂的吸收程度有差异,不等效.

Bioequivalence Evaluation of Domestic Simvastatin Tablets Compared with the Innovator Preparation in Chinese Healthy Volunteers

Objective： To study the relative bioavailability of domestic simvastatin tablets （test tablets） compared with the innova- tor preparation （ reference tablets） in Chinese healthy volunteers to evaluate the bioequivalence of the two products. Methods ： A single oral dose of 40 mg simvastation test tablets and reference tablets was given to 18 healthy volunteers in a randomized crossover study. The plasma concentration of simvastation was determined by LC-MS/MS. DAS 3.2.2 software was used tO calculate the pharmacokinet- ic parameters and evaluate the bioequivalence. Results ： After the oral administration, the major pharmacokinetic parameters of test tab- lets and reference tablets were as follows： t were （4.54 ±5.35） and （2.32 ± 1.72） h; Cmax were （5.63 ±4.03） and （7.29 ± 3.84） ng·ml-1;tv2 were （6.31 ±4.99） and （4.67 ±3.07） h;AUC（0-1）：（38.75±29.55） and （35.54 ±30.12）ng· h · ml-1; AUC（0-∞） were （67.31 ±60.25） and （40.36 ±34.78）ng · h · ml -1. The 90 % confidence interval ofAUC0→t was 89.5%-153.5% and AUC0→∞ was 118.1% -198.7% , both were beyond the standard of reference tablets （80%-125% ）. Conclusion： There is differ- ence in the relative bioavailability of the two tablets, and they are not bioequivalent.