柳氮磺吡啶肠溶片人体生物等效性研究

Study on bioequivalence of sulfasalazine enteric-coated tablet in healthy volunteers

目的柳氮磺吡啶肠溶片(sulfasalazine enteric-coated tablet,SECT)属于口服不易吸收的药物,其人体药动学和相对生物利用度研究存在一定难度。本研究通过评价不同厂家生产的两种制剂的生物等效性,建立SECT的研究方法。方法对24名健康男性志愿者按随机交叉自身对照的方法,给予单剂量口服500 mg SECT受试制剂和参比制剂,两次试验间隔为1周,分别测定血浆柳氮磺吡啶(sulfasalazine,SS)、磺胺吡啶(sulfapyridine,SP)、5-氨基水杨酸(5-aminosalicylic acid,5-ASA)浓度。结果血浆中SS、SP、5-ASA的药动学参数如下:以AUC_(0→t)计算,受试制剂SECT中SS相对生物利用度为(108.8±24.1)%;SP相对生物利用度为(105.0±25.0)%;5-ASA相对生物利用度为(94.1±22.0)%。以AUC_(0→∞)计算,受试制剂SECT中SS相对生物利用度为(106.9±23.4)%;SP相对生物利用度为(104.1±25.0)%;5-ASA相对生物利用度为(93.6±22.2)%。受试制剂与参比制剂的血药浓度-时间曲线基本一致,受试制剂与参比制剂主要药动学参数无显著性差异(P>0.05)。结论两家厂家生产的SECT,受试制剂与参比制剂在健康中国人体内具有生物等效性。

Objective To evaluate the pharmacokinetics and relative bioavailability of sulfasalazine enteric-coated tablets from two different factories in healthy volunteers. Methods 24 heahhy male volunteers were enrolled in the study. A single oral dose（500 mg） of test and reference Sulfasalazine Enteric-coated tablet preparations were given respectively to the volunteers according to random- ized two way cross over study design. The washout period was 1 week. The plasma concentrations of Sulfasalazine（SASP） and sulfapyridine（SP） were determined by HPLC-UV method, the plasma concentrations of 5-aminosalicylie acid （5-ASA） were determined by HPLC-FLU method. Results The pbarmacokinetic parameters of SASP, SP and 5-ASA in plasma were as follows： according to AUC0→t,the relative bioavailability of SASP,SPand5-ASA was （108.8±24.1）%, （105.0 ±25.0）% and （94.1±22.0）% in the test preparations ; while aecording to AUC0-→∞ , the relative bioavailability of SASP,SP and 5-ASA was （ 106.9± 23.4） % , （ 104.1 ± 25.0） % and （93.6± 22.2） % in the test preparations. Mean plasma concentration-time curve of the test product was highly close to that of the reference product. There was no significant difference in pharmacokinetic parameters between the test and reference preparations of sulfasalazine enteric-coated tablets （ P 〉 0. 05 ）. Conclusion The results of statistical analysis showed that the two sulfasalazine enteric-coated tablets from different factories in healthy volunteers were bioequivalent.