美沙拉秦生物等效评价标准的思考与建议  

Consideration and suggestion on bioequivalence standard of mesalamine

作　　者：刘鑫[1,2] 巨舸航 王欣桐 陈露露 欧阳冬生 LIU Xin;JU Ge-hang;WANG Xin-tong;CHEN Lu-lu;OUYANG Dong-sheng(Department of Clinical Pharmacology,Xiangya Hospital,Central South University,Changsha 410000,China;Changsha Duxact Biotech Co.,Ltd.,Changsha 410000,China;Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples,Changsha 410000,China)

机构地区：[1]中南大学湘雅医院临床药理研究所,长沙410000 [2]复杂基质样本生物分析湖南省重点实验室,长沙410000 [3]长沙都正生物科技股份有限公司,长沙410000

出　　处：《中国新药杂志》2023年第5期462-468,共7页Chinese Journal of New Drugs

基　　金：湖南省复杂基质样本生物分析国际科技创新合作基地资助项目(2019CB1014)。

摘　　要：美沙拉秦是一种能透过黏膜吸收进入体循环的胃肠道局部作用药物,目前为治疗轻度、中度溃疡性结肠炎的一线用药,其血药时间曲线可能反映药物的局部作用。但因其相关上市品种剂型规格繁多,包括缓释胶囊、肠溶片剂、栓剂、灌肠液等,通常采用的药动学终点指标血药峰浓度(C_(max))和血药浓度-时间曲线下面积(AUC)不一定能科学评价不同制剂美沙拉秦的质量一致性。本文综述了美国FDA、欧洲EMA对于美沙拉秦体内外生物等效性评价标准的制定和建议方案,并就我国公布的美沙拉秦参比制剂本身药学特征,总结发现我国公布的美沙拉秦参比制剂莎尔福并不适宜参照美国FDA所提出的美沙拉秦肠溶片生物等效性标准进行评价,并对此药提出了相应生物等效性评价指标选择的建议,以期为我国美沙拉秦仿制药的一致性评价工作提供参考。Mesalamine is a locally-acting gastrointestinal drug,which can be absorbed into the systemic circulation.It’s one of the first-class drugs for treating mild and moderate ulcerative colitis.Its plasma concentration-time curve reflects the locally acting effect of mesalamine;however,the commonly used pharmacokinetic parameters(AUC&C_(max))are insufficient to prove the bioequivalence of different preparations,due to the variation between different dosage forms,such as extended-release capsules,enteric-coated tablets,suppositories,and enemas.In this review,we summarizes the bioequivalence guidelines of different mesalamine preparations published by the U.S.Food and Drug Administration and European Medicines Agency.We also propose some suggestions for the bioequivalence standards of mesalamine based on the characteristics of its reference preparations in China.

关 键 词：美沙拉秦 仿制药 生物等效性 一致性评价 指导原则 

分 类 号：R975[医药卫生—药品]