国产左乙拉西坦片的人体生物等效性试验  

Bioequivalence test of domestic levetiracetam tablets in healthy volunteers

作　　者：邓鸣[1] 马婧怡[1] 孟令杰[1] 李育巧 郭欲晓 易崇勤 刘会臣[1] 

机构地区：[1]航天中心医院临床药理室,北京100049 [2]方正医药研究院,北京102206

出　　处：《中国新药杂志》2016年第19期2234-2239,共6页Chinese Journal of New Drugs

摘　　要：目的：研究在空腹和餐后条件下国产左乙拉西坦片的生物等效性,并探讨餐后给药试验的意义和样本量对试验结果的影响。方法：分别进行空腹和餐后单次给药的二交叉生物等效性试验,22名健康男性受试者口服国产左乙拉西坦片（受试制剂）或进口左乙拉西坦片（参比制剂）0.5 g,液相色谱-串联质谱联用法测定血浆中左乙拉西坦的浓度。采用Win Nonlin 6.4软件,非房室模型法计算药动学参数,药动学参数AUC和Cmax对数转换后,以90%置信区间（90%CI）法进行生物等效性评价。结果：在空腹和餐后条件下,健康男性受试者口服国产和进口左乙拉西坦片后左拉西坦的AUC0-t,AUC0-∞和Cmax几何均数比值（GMR）的90%CI均在80.00%-125.00%的范围内。与空腹给药相比,餐后给药后Tmax延长,Cmax降低,而AUC和t1/2没有差异。结论：在空腹和餐后条件下国产和进口左乙拉西坦片具有生物等效性;左乙拉西坦片的生物等效性试验可仅进行空腹试验,且12例样本量即可。Objective： To assess the bioequivalence of domestic levetiracetam tablets under fasting and fed conditions,and discuss the significance of the fed study and the effect of sample size on the test results. Methods：In two consecutive randomized,two-way,crossover studies,22 healthy male volunteers were given a single oral dose of 0. 5 g of domestic and imported levetiracetam tablets under fasting and fed conditions,respectively.Levetiracetam in plasma were determined by LC-MS / MS method. By means of Win Nonlin 6. 4 software,pharmacokinetic parameters were calculated using a non-compartmental model. The 90% confidence intervals（ 90% CI） of the test-to-reference geometric mean ratio（ GMR） of AUC and Cmaxwere calculated to assess the bioequivalence. Results： The 90% CI of the GMR of AUC0 - t,AUC0 - ∞and Cmaxbetween the test and reference fell within the limits of 80. 00% - 125. 00% under fasting and fed conditions,respectively. Food did not affect the AUC or t1 /2of levetiracetam,but decreased the Cmaxand delayed the Tmax. Conclusion： The domestic levetiracetam tablets were demonstrated to be equivalent to imported levetiracetam tablets under both fasting and fed conditions.The bioequivalence test of levetiracetam tablets can be conducted under only fasting conditions,and the power is sufficient for the bioequivalence assessment at the sample size of 12.

关 键 词：左乙拉西坦 空腹 饮食 液相色谱-串联质谱联用法 生物等效性 样本量 

分 类 号：R969[医药卫生—药理学]