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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(0-∞):(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→t90%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 investigate the bioavailability of domestic simvastatin tablets and the original preparation and to evaluate the bioequivalence of the two preparations in healthy volunteers. METHODS: Eighteen healthy adult male volunteers were randomized, crossover, controlled trials. A single oral dose of 40 mg of simvastatin tablets was used to determine plasma concentrations of simvastatin by LC-MS / MS. DAS 3.2.2 program was used to fit Pharmacokinetic parameters, and bioequivalence assessment. RESULTS: The main pharmacokinetic parameters of the two drugs were tmax (4.54 ± 5.35) and (2.32 ± 1.72) h, respectively, after a single oral dose of 40 mg simvastatin (domestic) and reference formulation. Cmax: (5.63 ± 4.01 ± 4.99) and (4.67 ± 3.07) h; AUC (0-t) :( 38.75 ± 29.55) and (35.54 ± 30.12) ng · H · ml-1; AUC (0-∞) :( 67.31 ± 60.25) and (40.36 ± 34.78) ng · h · ml-1. The relative bioavailability of the test preparation compared to the reference preparation was 117.2%. The AUC0 → t90% confidence limits of the test preparations ranged from 89.5% to 153.5%. The AUC0 → ∞90% confidence limits ranged from 118.1% to 198.7%, falling outside the range of 80% to 125% of the corresponding parameters of the reference formulation. Conclusion: There are differences between the absorption of the two preparations, not equivalent.