药代动力学研究在经口吸入制剂生物等效性评价中的应用进展  

Application and progress of pharmacokinetics study in bioequivalence evaluation of orally inhaled drug products

作　　者：张继胜 黄凯 储楠楠 贺晴 ZHANG Jisheng;HUANG Kai;CHU Nannan;HE Qing(Wuxi Clinical Medical School of Nanjing Medical University,Wuxi 214023,Jiangsu,China;Drug Clinical Trial Institute of Wuxi People's Hospital affiliated to Nanjing Medical University,Wuxi 214023,Jiangsu,China)

机构地区：[1]南京医科大学无锡临床医学院,江苏无锡214023 [2]南京医科大学附属无锡人民医院药物临床试验机构,江苏无锡214023

出　　处：《中国临床药理学与治疗学》2020年第11期1295-1308,共14页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：无锡市新药及医疗器械临床研究及评价公共服务平台(GGFWPT2019)。

摘　　要：经口吸入制剂在哮喘和慢性阻塞性肺疾病的药物治疗中有着举足轻重的地位和极大的临床需求。开发与原研药具有相同的有效性、安全性且更为经济的国产仿制药,有助于解决药品的可及性问题,也能极大减轻国家的公共卫生负担。经口吸入制剂是一类药械组合复杂制剂,且具有药物递送和局部作用的特殊性,仿制药的开发及注册难度大。目前美国食品药品监督管理局(Food and Drug Administration,FDA)、加拿大卫生部(Health Canada,HC)、欧洲药品协会(European Medicines Association,EMA)以及我国国家药品监督管理局(National Medical Products Administration,NMPA)所推荐的经口吸入制剂生物等效性评价方法不尽相同,均认为药代动力学研究可评价经口吸入制剂在人体内的全身暴露(安全性),但对于其在肺部沉积(有效性)研究中的作用尚未达成共识,原因是经口吸入制剂的疗效不仅由其肺部沉积量决定,还与肺部沉积区域有关。但相比于药效学/临床终点研究,药代动力学研究在评价制剂间的潜在差异上更灵敏更经济。本文主要对经口吸入制剂生物等效性研究的国内外指导原则和评价方法进行比较,并对药代动力学研究的试验设计及其在肺部沉积研究中的应用进展进行介绍。Orally inhaled drug products(OIDPs)have a pivotal position and great clinical demand in the treatment of asthma and chronic obstructive pulmonary disease.The development of local generic drugs which are bioequivalent to branded drugs in efficacy and safety while with less price will not only help to solve the problem of drug accessibility,but also greatly reduce the public health burden.OIDPs are complex combinations of formulation and device,and have special drug delivery route and characteristic of local release.Thus,generic drugs of OIDPs are difficult to develop and get registration.Until now,Food and Drug Administration(FDA),European Medicines Association(EMA),Health Canada(HC)and National Medical Products Administration(NMPA)all consider that pharmacokinetics(PK)method can be used to evaluate systemic exposure(safety)in human bioequivalence(BE)study of OIDPs,but there is no consensus on its role in the evaluation of pulmonary deposition(efficacy).The possible reason lies in that the efficacy of OIDPs is determined by both the amount and the region of drug pulmonary deposition.Nevertheless,PK study is still more sensitive and economical in assessing potential differences among products,when compared with pharmacodynamics or clinical endpoint study.Here we mainly compared the domestic and international guidelines and evaluation methods of OIDPs BE study,and introduced the experimental design of PK study and its application and progress in lung deposition study.

关 键 词：经口吸入制剂 生物等效性 药代动力学 药品监管机构 

分 类 号：R969.1[医药卫生—药理学]