司他夫定片在人体药动学和相对生物利用度研究

 目的研究司他夫定片剂的健康人体药动学和相对生物利用度。方法采用高效液相色谱法测定20名健康志愿者自身交叉、单剂量口服司他夫定胶囊和片剂各40mg后血浆司他夫定浓度。用3P97药动学软件进行药动学参数计算及生物等效性评价。结果两种司他夫定的药-时曲线均符合一房室模型,参比制剂、被试制剂的主要药动学参数如下:ρ_max分别为(1.01±0.24)和(0.95±0.30)mg·L^-1;t_max分别为(0.78±0.22)和(0.70±0.21)h;t_1/2ke分别为(1.47±0.22)和(1.47±0.23)h;AUC_0～t分别为(2.21±0.46)和(2.08±0.53)mg·h·L^-1;AUC_0～∞分别为(2.33±0.53)和(2.16±0.58)mg·h·L^-1。与标准参比制剂相比,被试制别的相对生物利用度F_0～t为(97.02±27.71)%,F_0～∞为(96.33±29.51)%。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。结论司他夫定胶囊和片剂具有生物等效性。

Pharmacokinetics and relative bioavailability study of stavudine in healthy volunteers

OBJECTIVE To evaluate the pharmacokineties and relative bioavailability of two stavudine preparations in healthy volunteers. METHODS A single oral dose 40 mg of stavudine preparations, capsule and tablet, was given to 20 healthy volunteers in a randomized cross-over study. The concentration of stavudine in plasma was determined by HPLC method with UV detector. RESULTS The concentrationtime curves were fitted to a one-compartment open model. The main pharmacokinetic parameters of stavudine capsule and tablet were as follows:ρ_max were(1.01±0.24) and (0.95±0.30)mg·L^-1; t_max were(0.78±0.22) and (0.70±0.21 )h;t_1/2ke were (1.47±0.22) and (1.47±0.23)h; AUC_0～t were (2.21±0.46) and (2.08±0.53) mg·h·L^-1; AUC_0～∞ were (2.33±0.53) and (2.16±0.58) mg·h·L^-1. The relative bioavalability of F_0～t and F_0～∞ were (97.02±27.71)% and (96.33±29.51)%, respectively. The results of ANOVA and two onesided t test statistical analysis showed that two formulations were bioequivalent. CONCLUSION The results showed that two stavudine preparatians were bioequivalent.