缬沙坦分散片与胶囊在健康人体的相对生物利用度研究

Relative bioavailability of valsartan dispersible tablets and valsartan capsules in healthy volunteers

目的 研究缬沙坦分散片和胶囊在人体内的相对生物利用度。方法 18名健康志愿者,采用自身对照,随机交叉方式分别口服缬沙坦分散片或胶囊160 mg后不同时间点取血,血浆样品以新建立的高效液相色谱-荧光检测法测定,比较两者主要药物动力学参数的差异和相对生物利用度。结果 缬沙坦分散片和胶囊的AUC0-30均值分别为(17 268.2±5 611.6)、(17 723.1±5 844.2)μg·h·L-1,cmax均值分别为(2 185.9±656.9)、 (2 176.5±730.7)μg·L-1,实测tmax均值分别为(1.2±0.5)、(2.2±0.4)h,方差分析结果表明,两种制剂的AUC0-∞、cmax没有显著性差异(P>0.05),两制剂间的tmax有显著差异(P<0.05),分散片明显快于胶囊剂。以胶囊为参比制剂,缬沙坦分散片的相对生物利用度为(98.8±14.6)％。结论 缬沙坦分散片体内吸收快于缬沙坦胶囊,但血药浓度峰值和吸收程度没有显著性差异,两者仍具有生物等效性。

OBJECTIVE To compare the absorption rate and observe the relative bioavailability of valsartan dispers ible tablets and capsules. METHODS A single oral dose of 160 mg dispersible tablets or capsules were given to 18 healthy volunteers in a randomized crossover study. The concentrations of valsartan were determined by newly developed HPLC method with fluorimetric detection. Parameters were obtained from the plasma concentration - time curve, and pharmacokinetics/relative bioavailability were studied. RESULTS The main pharmacokinetics parameters of the two products were as follows: AUC0~30 (17 268. 2±5 611. 6) μg · h · L-1and (17 723. 1 ± 5 844. 2) μg · h· L-1, cmax (2185.9 ± 656.9) μg·L-1 and (2176.5 ± 730.7) μg · L-1, tmax (1.2 ± 0.5) h and (2.2 ± 0.4) h, respectively. The absorption rate of valsartan dispersible tablets was higher than that of valsartan capsules. The relative bioavailability of dispersible tablets to capsules was (98. 8 ± 14. 6)%. CONCLUSIONS There are significant differences in the absorption rate but no significant difference in other parameters between the two preparations (P>0. 05) . The results demonstrated that the two preparations are bioeqivalent.