缬沙坦3种制剂的健康人体生物等效性研究

Bioequivalence study of three kinds of valsartan preparations in healthy volunteers

目的 :研究缬沙坦 3种制剂的人体生物利用度和药动学特征。方法 :2 4名健康男性受试者采用三制剂三周期随机交叉试验设计 ,分别口服单剂量 80mg缬沙坦片剂 (被试制剂T 1)、胶囊 (被试制剂T 2 )和缬沙坦胶囊 (参比制剂R)。采用HPLC 荧光检测法测定血浆样品中的缬沙坦浓度。结果 :T 1,T 2与R的主要药动学参数分别为 :Tmax(2 .4±s 0 .8)h ,(2 .8± 0 .8)h和 (2 .2± 0 .5 )h ;Cmax(2 .2± 0 .8)mg·L- 1,(1.9± 1.0 )mg·L- 1和 (2 .0± 1.0 )mg·L- 1;AUC0 2 4 (12± 4 )mg·h·L- 1,(11± 4 )mg·h·L- 1和 (11± 5 )mg·h·L- 1;T12 β(6 .0± 1.1)h ,(5 .8± 1.0 )h和 (5 .9± 0 .9)h。相对生物利用度 :(117± 37) % (T 1)和 (10 4± 4 4) % (T 2 )。药动学参数经多因素方差分析显示周期间与制剂间差异均无显著意义 (P >0 .0 5 ) ,双单侧t检验表明接受T 1与R和T 2与R生物等效的假设 ,经计算 90 %置信区间均在规定值内。结论 :T 1,T 2与R

AIM: To study the relative bioavailability and the pharmacokinetics of three kinds of valsartan preparations. METHODS: This is an open randomized , three period crossover study on twenty four healthy volunteers after a single oral dose of 80 mg valsartan as tablet (T 1),capsule(T 2) and reference (R). A method of HPLC and fluorescence detection was established to determine the concerntrations of valsartan in plasma. RESULTS: The main pharmacokinetic parameters of T 1, T 2 and R were as follows: T max (2.4± s 0.8) h, (2.8±0.8) h and (2.2 ± 0.5) h; C max (2.2±0.8) mg·L -1 , (1.9±1.0) mg·L -1 and (2.0±1.0) mg·L -1 ; AUC 0 24 (12±4) mg·h·L -1 , (11±4) mg·h·L -1 and (11±5) mg·h·L -1 ; T 12β (6.0±1.1) h,(5.8±1.0) h and (5.9 ± 0.9 ) h. The relative bioavailability of test drug was (117±37)% (T 1) and (104±44)% (T 2). The result of ANOVA and two one side t test statistical analysis showed that there were no significant differences among T 1,T 2 and R( P > 0.05). The 90% confidence interval was in the regulated range. CONCLUSION: T 1,T 2 and R are bioequivalent.