摘要
吸入制剂和纳米注射剂给药后在靶器官富集发挥作用,其体内药动学行为和效应/毒性器官暴露量之间缺乏相关性,因此,仅凭经典药动学研究不足以评价其仿制制剂的生物等效性。对此,FDA已明确要求首先采用群体生物等效性方法进行体外研究,结合药动学指标和临床终点指标共同评价仿制制剂的安全性和有效性。本文着重介绍了FDA对于这2类制剂的体外群体生物等效性研究方法,并根据指导文件重现了吸入用布地奈德混悬液的等效性结果。此外,还进一步推算了受试制剂与参比制剂的等效粒径分布范围。该研究有助于在仿制药工艺研究阶段,帮助制剂研究人员确定目标制剂的理化性质、优化制剂工艺设计,确保具有较高可信度的制剂进入临床阶段并缩短药物研发周期,从而提升我国特殊制剂的一致性研究水平。
Demonstrating bioequivalence(BE） for inhaled drug products and nanoparticulate intravenous formulations for local action has been very challenging with classical pharmacokinetic parameters alone because the relationship between the drug in systemic circulation and the drug reaching the site of action has not been well established. According to the current FDA guidance on bioequivalence studies for inhaled drug products and nanoparticulate intravenous formulations, bioequivalence should be established first by a number of in vitro population bioequivalence(PBE） tests that demonstrate equivalent product performance,subsequently by in vivo pharmacokinetic(PK） BE study and clinical endpoint study of the test and reference products. This paper introduces the statistical rationale of related guidelines in PBE calculation,and demonstrates the process of the PBE calculation of budesonide suspension inhalation. In addition,equivalent range of particle size distribution of the test and reference products has been provided based on the PBE results. The researchers may adjust the pharmaceutical process accordingly so that a more credible formulation for clinical trials could be obtained with less time consuming exploration. It is believed that the application of PBE study for inhaled drug products and nanoparticulate intravenous formulations for local action would greatly accelerate the development of complex generic drugs in China.
作者
臧云娜
俞森
杨劲
ZANG Yun-na;YU Sen;YANG Jin(China Pharmaceutical University,Nanjing 210009 ,China;Shanghai Mosim Co., Ltd. ,Shanghai 201203, China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2018年第10期1116-1121,共6页
Chinese Journal of New Drugs
关键词
吸入制剂
纳米注射剂
体外群体生物等效性
粒径分布
仿制药
inhaled drug products
nanoparticulate intravenous formulations
in vitro population bioequivalence
particle size distribution
generic drug
