国产辛伐他汀片与原研制剂的生物等效性研究

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

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.

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.