皮肤药动学在经皮给药制剂生物等效性评价中的研究进展  

Advances of dermato-pharmacokinetic in the bioequivalence assessment of topical formulation

作　　者：刘晓琳 丁亮 管宴萍 黄民[1,2] 钟国平 LIU Xiao-lin;DING Liang;GUAN Yan-ping;HUANG Min;ZHONG Guo-ping(Institute of Clinical Pharmacology,School of Pharmaceutical Sciences,Sun Yat-Sen University,Guangzhou 510080,China;Guangdong Engineering Technology Research Center of Quality Consistency Evaluation for Generic Drugs,Guangzhou 510080,China;People's Hospital of Baoan District,Shenzhen 518101,China;Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China)

机构地区：[1]中山大学药学院临床药理研究所,广州510080 [2]广东省仿制药一致性评价工程技术研究中心,广州510080 [3]深圳市宝安区人民医院临床试验研究中心,深圳518101 [4]中山大学孙逸仙纪念医院,广州510120

出　　处：《中国新药杂志》2020年第23期2683-2689,共7页Chinese Journal of New Drugs

基　　金：广东省科技发展专项基金资助项目(2016A040403047)。

摘　　要：局部皮肤外用制剂因其给药方式的特殊性,在进行生物等效性(bioequivalence,BE)研究时需根据药物本身的特点和作用部位采用不同的研究方法。目前应用较广泛的体内药动学(pharmacokinetics,PK)方法、体内药效学(pharmacodynamics,PD)方法、临床终点法等均存在一定的局限性。本文重点介绍了皮肤药物代谢动力学(dermato-pharmacokinetic,DPK)的原理及方法,讨论应用经皮水分散失值(trans-epidermal water loss,TEWL)法及其优化方法在局部经皮给药制剂生物等效性/生物利用度评价中的优势及研究进展,探讨其成为生物等效性替代评估法的可能性。针对DPK方法的标准操作规程和方法学确证需得到进一步的发展,以促进稳健的经皮给药制剂生物等效性评价方法的开发。The bioequivalence(BE) assessment is quite difficult for topical dermatological products due to their variable characteristics and effective sites.All of the widely used approaches for determination of BE,such as in vivo pharmacokinetics(PK),in vivo pharmacodynamics(PD) and clinical end-points,have certain limitations when applied to topical formulations.The aim of this article is to introduce the basic mechanism of dermato-pharmacokinetic(DPK),and the approach of trans-epidermal water loss(TEWL),including its advances and optimization,in order to discuss its potential in BE assessment of topical dermatological drugs in the future.The standard operating procedures and methodology for the DPK method need to be further developed to promote the development of a robust method for evaluating the bioequivalence of dermatological drug products.

关 键 词：皮肤药物代谢动力学 局部经皮给药制剂 生物等效性 

分 类 号：R969.1[医药卫生—药理学]