2种伏立康唑片剂的人体生物等效性研究

Bioequivalence of two voriconazole tablets in healthy volunteers

目的：研究2种伏立康唑片剂在健康志愿者体内的相对生物利用度。方法：采用双周期自身随机交叉试验设计。20名健康男性志愿者单剂量口服试验制剂或参比制荆200mg，血浆样品采用高效液相色谱-质谱-质谱测定。用3P97对药动学参数进行方差分析及双单侧t检验。结果：伏立康唑血药浓度在20～2000μg·L^-1范围内线性关系良好（r=0．9993），最低定量浓度为20μg·L^-1，相对回收率为（92．86±3．54）％，日内及日间RSD〈6％。试验制剂及参比制剂的伏立康唑片Cmax分别为（1640．05±564．77）和（1772．08±676．26）μg·L^-1；Tmax分别为（1．30±0．81）和（1．10±0．65）h；试验制剂及参比制剂t1／2（ke）分别为（6．92±2．56）和（7．23±3．11）h；AUC0-tn平均值分别为（8827．99±4243．32）和（8122．76±3740．72）μg·h·L^-1AUC0-∞平均值分别为（9966．79±5415．76）和（9393．36±5025．56）μg·h·L^-1；试验制剂伏立康唑片的相对生物利用度F0-tn，R0-∞分别为（109．28±17．96）％和（107．53±20．87）％。结论：试验制剂和参比制剂具有生物等效性。

Objective：To evaluate relative bioavailability of voriconazole tablets in healthy volunteers, nethods：A single oral dose was given respectively to 20 healthy volunteers in a two-way cross over test to study the pharmacokinetics of voriconazole. The concentration was determined by HPLC-MS- MS. 3P97 was used to analyze the pharmacokinetic parameters. Results：The linear range of voriconazole in plasma was from 20 to 2 000μg·L^-1 （ r = 0. 999 3 ） and the limit of detection was 20μg·L^-1. The related recovery was （92.86 ±3.54）% ,the intra- and inter-day precision were all less than 6%. The main pharmaeokinetic parameters of test preparation and reference preparation were as follows： Cmax （1 640,05 ±564.77） and （1 772.08 ±676.26）μg·L^-1 ,Tmax（1.30 ±0.81） and （1.10 ±0.65） h,t1/2（ke）（6.92±2.56）and （7.23 ±3.11）h,AUCo0-tn（8 827.99±4243.32）and （8 122.76±3 740.72）μg·h·L^-1,AUC0-∞（9966.79±5415.76）and （9393.36±5025.56）μg·h·L^-1. F0-tn and F0-∞ of test preparation were （109.28 ± 17.96）% and （107.53 ±20.87）%. Conclusion：The results of statistical analysis shows the two prepareations are bioequivalent.