国产奈韦拉平片健康人体相对生物利用度研究

Pharmacokinetics and Relative Bioavailability Study of Nevirapine in Healthy Volunteers

目的研究国产奈韦拉平片健康人体相对生物利用度。方法采用双周期自身交叉对照试验设计,20名健康志愿者po国产和进口奈韦拉平片各200 mg后采用高效液相色谱法测定血浆药物浓度。用3P97药动学软件进行药动学参数计算及生物等效性评价。结果两种奈韦拉平片的药-时曲线均符合一房室模型,参比制剂、受试制剂的主要药动学参数如下：t_(max)分别为(3.50±1.05)和(4.20±1.24)h；ρ_(max)分别为(2394±392)和(2170±434)μg·L^(-1)。,t_(1/2ka)分别为(0.85±1.00)和(0.79±0.51)h,t_(1/2ke)分别为(52.30±13.82)和(55.59±10.51)h；AUC_(0～t)分别为(149.20±30.54)和(154.05±27.77)mg·h·L^(-1),AUC_(0-∞)分别为(168.30±40.22)和(173.30±36.65)mg·h·L^(-1)。与标准参比制剂相比,受试制剂的相对生物利用度F_(0-t)为(104.97±16.51)%,F_(0-∞)为(105.21±18.93)%。对两制剂间的AUC_(0～t),AUC_(0～∞)和ρ_(max)进行双向单侧t检验,表明两种制剂具有生物等效性。结论国产和进口奈韦拉平片具有生物等效性。

OBJECTIVE To evaluate relative bioavailability of domestic nevirapine in healthy volunteers. METHODS A single oral dose of 200 mg nevirapine domestic and imported tablets, was given to 20 health volunteers in a randomized cross-over study. The nevirapine concentrations in plasma were determined by HPLC method. RESULTS The concentrations of two formulations were fitted to an one-compartment open model. The main pharmacokinetic parameters of two nevirapine tablets were as follows： tmax （3.50 ± 1.05 ）and（4.20 ± 1.24） h; ρmax were（2 394±392）and（2 170±434） μg·L^-1; t1/2ka（0.85± 1.00） and （0.79±0.51） h;t1/2ke（52.30± 13.82） and （55.59± 10.51） h; AUC0-t（149.20±30.54） and （154.05±27.77） mg·h·L^-1;AUC0-∞ （168.30±40.22） and （173.30±36.65） mg·h·L^-1 respectiely. The relative bioavalability of F0-t and F0-∞ （ 104.97± 16.51 ） % and （ 105.21 ± 18.93 ） %, respectively. CONCLUSION The ANOVA and two one-sided t test statistical analysis show that two formulations are bioequivalent.