Nielsen Jesper Bo, Benfeldt Eva, Holmgaard Rikke
Curr Probl Dermatol. 2016;49:103-11. doi: 10.1159/000441549. Epub 2016 Feb 4.
The skin is a strong and flexible organ with barrier properties essential for maintaining homeostasis and thereby human life. Characterizing this barrier is the ability to prevent some chemicals from crossing the barrier while allowing others, including medicinal products, to pass at varying rates. During recent decades, the latter has received increased attention as a route for intentionally delivering drugs to patients. This has stimulated research in methods for sampling, measuring and predicting percutaneous penetration. Previous chapters have described how different endogenous, genetic and exogenous factors may affect barrier characteristics. The present chapter introduces the theory for barrier penetration (Fick's law), and describes and discusses different methods for measuring the kinetics of percutaneous penetration of chemicals, including in vitro methods (static and flow-through diffusion cells) as well as in vivo methods (microdialysis and microperfusion). Then follows a discussion with examples of how different characteristics of the skin (age, site and integrity) and of the penetrants (size, solubility, ionization, logPow and vehicles) affect the kinetics of percutaneous penetration. Finally, a short discussion of the advantages and challenges of each method is provided, which will hopefully allow the reader to improve decision making and treatment planning, as well as the evaluation of experimental studies of percutaneous penetration of chemicals.
皮肤是一个强大且具有柔韧性的器官，具有屏障特性，这对于维持体内平衡乃至人类生命至关重要。表征这种屏障的能力在于能够阻止某些化学物质穿过屏障，同时允许其他物质（包括药品）以不同速率通过。在最近几十年中，后者作为一种向患者有意给药的途径受到了越来越多的关注。这刺激了对采样、测量和预测经皮渗透方法的研究。前面的章节已经描述了不同的内源性、遗传性和外源性因素如何影响屏障特性。本章介绍了屏障渗透理论（菲克定律），并描述和讨论了测量化学物质经皮渗透动力学的不同方法，包括体外方法（静态和流通扩散池）以及体内方法（微透析和微灌注）。接着通过实例讨论皮肤的不同特性（年龄、部位和完整性）以及渗透剂的不同特性（大小、溶解度、电离、脂水分配系数和载体）如何影响经皮渗透动力学。最后，对每种方法的优点和挑战进行了简短讨论，希望能帮助读者改进决策制定和治疗规划，以及对化学物质经皮渗透实验研究的评估。
