复方磺胺甲噁唑片在中国健康志愿者中的药动学及生物等效性研究  

Pharmacokinetics and bioequivalence of compound sulfamethoxazole tablets in Chinese healthy volunteers

作　　者：冯仕银 陈卓[1,2] 蔡林芮[1,2] 余勤[1,2] 苏旭 邹琴 郭伟一[1,2] 王晶[1,2] 陈冠华[3] 蒋红梅 陆纪宏 施华琴[3] FENG Shi-yin;CHEN Zhuo;CAI Lin-rui;YU Qin;SU Xu;ZOU Qin;GUO Wei-yi;WANG Jing;CHEN Guan-hua;JIANG Hong-mei;LU Ji-hong;SHI Hua-qin(Institute of Drug Clinical Trial·GCP,West China Second University Hospital,Sichuan University,Chengdu 610041,China;Key Laboratory of Birth Defects and Related Diseases of Women and Children,Sichuan University,Ministry of Education,Chengdu 610041,China;Zhejiang Jinhua Conba Biopharm Co. ,Ltd. ,Jinhua 321016,China)

机构地区：[1]四川大学华西第二医院国家药物临床试验机构,成都610041 [2]出生缺陷与相关妇儿疾病教育部重点实验室(四川大学),成都610041 [3]浙江金华康恩贝生物制药有限公司,金华321016

出　　处：《中国新药杂志》2019年第16期2019-2024,共6页Chinese Journal of New Drugs

摘　　要：目的:研究中国健康志愿者空腹单次口服复方磺胺甲噁唑片的人体药动学特征,评价复方磺胺甲噁唑片受试制剂与参比制剂中的磺胺甲噁唑和甲氧苄啶的生物等效性。方法:采用开放、随机、双周期、交叉设计,32例健康志愿者空腹条件下口服复方磺胺甲噁唑片(磺胺甲噁唑0.4 g,甲氧苄啶80 mg)受试制剂和参比制剂后,采用LC-MS/MS法测定磺胺甲噁唑、甲氧苄啶的血药浓度。使用Phoenix WinNonlin 7.0版中的非房室模型分析,计算药动学参数并评价2种复方磺胺甲噁唑片中磺胺甲噁唑和甲氧苄啶的生物等效性。结果:空腹条件下中国健康志愿者口服受试制剂和参比制剂后磺胺甲噁唑的受试制剂与参比制剂Cmax,AUC0~t,AUC0~∞几何均值比值的90%置信区间分别为99.29%~104.13%,98.87%~103.04%,98.76%~103.14%,符合80.00%~125.00%的范围;甲氧苄啶的受试制剂与参比制剂Cmax,AUC0~t,AUC0~∞几何均值比值的90%置信区间分别为95.89%~105.37%,98.40%~104.47%,98.42%~104.00%,符合80.00%~125.00%的范围。结论:在空腹条件下磺胺甲噁唑、甲氧苄啶受试制剂与参比制剂具有生物等效性。Objective: To study the pharmacokinetic characteristics and bioequivalence of compound sulfamethoxazole tablets in healthy volunteers. Methods: An open,randomized,two-phases and crossover experiment was performed in 32 Chinese healthy volunteers. The volunteers were given a single oral dose of domestic or imported compound sulfamethoxazole tablet (sulfamethoxazole 0. 4 g, trimethoprim 80 mg) under fasting conditions.Sulfamethoxazole and trimethoprim in plasma were determined by LC-MS/MS method. Using Phoenix WinNonlin7. 0 software,the pharmacokinetic parameters and bioequivalence of sulfamethoxazole and trimethoprim were calculated using a non-compartmental model. Results: For sulfamethoxazole,the 90% CIs of the GMR of Cmax,AUC0 ~ t and AUC0 ~ ∞ between the test and reference drug were 99. 29% ~ 104. 13%,98. 87% ~ 103. 04%,and 98. 76% ~ 103. 14%,respectively,falling within the limit range of 80. 00% ~ 125. 00%. For trimethoprim,the 90%CIs of the GMR of Cmax,AUC0 ~ t and AUC0 ~ ∞ between the test and reference drug were 95. 89% ~ 105. 37%,98. 40% ~ 104. 47%,and 98. 42% ~ 104. 00%,respectively,falling within the limit range of 80. 00% ~ 125. 00%.Conclusion: The domestic compound sulfamethoxazole tablets are proved to be bioequivalent to imported compoundsulfamethoxazole tablets under fasting conditions.

关 键 词：磺胺甲噁唑 甲氧苄啶 空腹 LC-MS/MS 生物等效性 

分 类 号：R969.1[医药卫生—药理学]