He Hua, Yuan Dongfen, Wu Yun, Cao Yanguang
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Pharmaceutics. 2019 Mar 7;11(3):110. doi: 10.3390/pharmaceutics11030110.
Liposomal formulations have been developed to improve the therapeutic index of encapsulated drugs by altering the balance of on- and off-targeted distribution. The improved therapeutic efficacy of liposomal drugs is primarily attributed to enhanced distribution at the sites of action. The targeted distribution of liposomal drugs depends not only on the physicochemical properties of the liposomes, but also on multiple components of the biological system. Pharmacokinetic⁻pharmacodynamic (PK⁻PD) modeling has recently emerged as a useful tool with which to assess the impact of formulation- and system-specific factors on the targeted disposition and therapeutic efficacy of liposomal drugs. The use of PK⁻PD modeling to facilitate the development and regulatory reviews of generic versions of liposomal drugs recently drew the attention of the U.S. Food and Drug Administration. The present review summarizes the physiological factors that affect the targeted delivery of liposomal drugs, challenges that influence the development and regulation of liposomal drugs, and the application of PK⁻PD modeling and simulation systems to address these challenges.
脂质体制剂已被开发出来，通过改变靶向和非靶向分布的平衡来提高包封药物的治疗指数。脂质体药物治疗效果的提高主要归因于其在作用部位分布的增强。脂质体药物的靶向分布不仅取决于脂质体的物理化学性质，还取决于生物系统的多个组成部分。药代动力学-药效学（PK-PD）建模最近已成为一种有用的工具，可用于评估制剂和系统特异性因素对脂质体药物靶向处置和治疗效果的影响。使用PK-PD建模来促进脂质体药物仿制药的开发和监管审查最近引起了美国食品药品监督管理局的关注。本综述总结了影响脂质体药物靶向递送的生理因素、影响脂质体药物开发和监管的挑战，以及PK-PD建模和模拟系统在应对这些挑战方面的应用。
