摘要
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.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2007年第14期1133-1136,共4页
Chinese Journal of New Drugs