健康志愿者恩替卡韦分散片的生物等效性研究

目的评价2种恩替卡韦制剂在健康人体的生物等效性。方法采用随机、双周期、自身交叉的试验设计。36例健康男性志愿者单次口服试验制剂（恩替卡韦分散片）或参比制剂（恩替卡韦片）1 mg,血浆样品采用高效液相色谱-串联质谱法（HPLC-MS/MS）测定,计算两者的主要药物动力学参数,进行生物等效性评价。结果恩替卡韦血药浓度在0.05～20μg.L-1与峰面积线性关系良好（R2=0.996 3）,最低定量浓度为0.05μg.L-1,批内及批间精密度RSD〈15%;服用试验制剂或参比制剂后血浆中恩替卡韦的Cmax分别为（7.63±1.91）和（9.75±2.62）μg.L-1;tmax分别为（0.67±0.22）和（0.63±0.19）h;t1/2分别为（62.35±22.36）和（62.09±33.39）h;AUC0-∞分别为（29.08±4.57）和（31.88±6.57）μg.h.L-1;AUC0-tn分别（22.80±4.19）和（25.57±5.06）μg.h.L-1;试验制剂的相对生物利用F0-tn、F0-∞分别为（90.55±14.42）%和（93.36±15.96）%。结论试验制剂和参比制剂具有生物等效性。

Bioequivalent assessment of entecavir hydrochloride in healthy volunteers

Objective To evaluate the bioequivalence of entecavir hydrochloride dispersible tablets in healthy volunteers.Methods A single oral dose of entecavir hydrochloride test and reference preparations was given to 36 healthy volunteers,respectively,in a two-way cross-over test.The entecavir concentration was determined by HPLC-MS/MS.The pharmacokinetic parameters and bioequivalence of the two preparations were analyzed.Results The linear range of entecavir hydrochloride in the plasma was 0.05-20 μg·L-1（R2=0.996 3） and the limit of detection was 0.05 μg·L-1;the intra-and inter-day precision was less than 15%.The main pharmacokinetic parameters of the test and reference preparations were as follows：Cmax（7.63±1.91） and（9.75±2.62）μg·L-1;tmax（0.67±0.22） and（0.63±0.19） h;t1/2（62.35±22.36） and（62.09±33.39） h;AUC0-∞（29.08±4.57） and（31.88±6.57）μg·h·L-1;AUC0-tn（22.80±4.19）and（25.57±5.06） μg·h·L-1;F0-tn and F0-∞ of the test preparation were（90.55±14.42）% and（93.36±15.96）%.Conclusion The test preparation is bioequivalent to the reference preparation.