替米沙坦人体药动学及生物等效性研究

 目的　研究替米沙坦的药动学特征,评价国产替米沙坦片剂及胶囊的人体相对生物利用度。方法　三交叉实验设计;18名健康受试者随机分为3组,单剂量po替米沙坦 80mg,试验之间的清洗期为12d;高效液相色谱法测定血浆中替米沙坦浓度。结果 3种制剂的主要药动学参数无显著性差异,受试片剂、胶囊及参比制剂的c_max分别为(812.16±110.65),(819.54±129.97)和(855.37±92.27)ng·mL^-1;t_max分别为(0.99±0.43),(0.83±0.36)和 (1.15±0.61)h;t_{1/ 2}分别为(19.3±7.0),(19.5±2.9)和(18.6±3.9)h;AUC_0～72分别为(4181.43±2536.14),(3785.63±2477.71)和(3874.48±1981.11)ng·h·mL^-1。替米沙坦片剂及胶囊的生物利用度分别为(106.87±16.17)%和(97.69±20.65)%。结论　3种剂型的主要药动学参数经方差分析、双单侧t检验及90%可信限计算表明两种国产替米沙坦制剂与进口片剂生物等效。

Studies on pharmacokinetics and bioequivalence of telmisartan in healthy volunteers

OBJECTIVE To study the pharmacokinetics profiles of telmisartan and observe the bioavailability of domestic telmisartan tablet and capsule.METHODS A triple cross experiment design was conducted. 18 healthy volunteers were given a single dose of 80 mg telmisartan after divided into 3 groups randomly.The wash out period was 12 d .HPLC method was applied to analyze telmisartan concentration in plasma.RESULTS The main pharmacokinetics parameters of three preparations(tablet,capsule and reference) were as follow:c_maxwere(812.16±110.65),(819.54±129.97)and(855.37±92.27)ng·mL^-1;t_max were(0.99±0.43),(0.83±0.36)and(1.15±0.61)h;t_1/2 were(19.3±7.0),(19.5±2.9)and(18.6±3.9)h;AUC_0～72were(4181.43±2536.14),(3785.63±2477.71)and(3874.48±1981.11)ng·h·mL^-1,respectively.The bioavailability of tablet and capsule were (106.87±16.17)% and(97.69±20.65)%,respectively.CONCLUSION The pharmacokinetic figures were weighed with ANOVA,two one sided t test and 90% confidence interval and the results showed the two domestics preparations were both bioequivalent compared with the imported tablet.