对氨基水杨酸肠溶颗粒单次和多次给药人体药代动力学和生物等效性研究

Single-dose and multi-dose pharmacokinetics and bioavailability of para-aminosalicylic acid enteric granules

目的研究对氨基水杨酸肠溶颗粒单次和多次给药人体药代动力学特征和生物等效性。方法采用双周期自身交叉对照试验设计。空腹/餐后试验和多次给药试验各24名男性健康志愿者,分别单次或多次口服受试制剂或参比制剂4 g。采用HPLC法测定给药后不同时间对氨基水杨酸(PAS)的血药浓度,采用非房室模型药动学参数计算的方法求算药动学参数,并进行统计分析。结果单次给药试验:受试者口服试验药物和参比药物后血浆中PAS主要药代动力学参数Cmax、AUC0~24 h和AUC0~∞比值的90%置信区间均未超出80%~125%。不同制剂间tmax均无显著性差异(P>0.05)。餐后组与空腹组相比,tmax略有缩短,但Cmax、AUC0~24 h和AUC0~∞显著增加。多次给药试验:受试制剂与参比制剂PAS的Css-max和AUCss比值的90%置信区间均未超出80%~125%。不同制剂间tss-max均无显著性差异(P>0.05)。结论对氨基水杨酸肠溶颗粒试验制剂与参比制剂生物等效。

Objective To determine the single-dose and multi-dose pharmacokinetics and bioavailability of para-aminosalicylic acid enteric granules in Chinese healthy volunteers.Methods The tests were for open,randomized,crossover and two-cycle study.In the fasting/fed trial,another 24 male healthy volunteers took 4 g of test preparation or reference preparation each time.In the multiple dose trials,24 male healthy volunteers took the test preparation or reference preparation(4 g)many times.The plasma concentrations of para-aminosalicylic acid(PAS)at different time after the administration were determined by HPLC.The model of non-compartmental pharmacokinetic parameters was used to calculate the pharmacokinetic parameters,before statistical analysis.Results In the single dose test:the 90%CIs of Cmax,AUC0~24 h and AUC0~∞ratios(the main pharmacokinetic parameters of PAS)in the plasma of the subjects between the test and reference preparations fell in the limit ranges of 80%-125%under fasting and fed conditions,respectively.There was no significant difference in tmax between both preparations(P>0.05).Compared with that of the fasting test,tmax was slightly shorter in the fed test,but Cmax,AUC0~24 h and AUC0~∞were significantly increased.In the multiple dose trials:the 90%CIs of Css-max and AUCss ratios of PAS in the plasma of the subjects between the test and reference preparations fell in the limit ranges of 80%-125%.There was no significant difference in tss-max between both preparations(P>0.05).Conclusion Para-aminosalicylic acid enteric granule test preparations and the reference preparations are bioequivalent.