Frum Yakov, Eccleston Gillian M, Meidan Victor M
Division of Pharmaceutical Sciences, SIPBS, University of Strathclyde, Glasgow, UK.
Eur J Pharm Biopharm. 2007 Sep;67(2):434-9. doi: 10.1016/j.ejpb.2007.03.012. Epub 2007 Mar 18.
Over recent decades, the use of in vitro diffusion cell studies to assess skin permeability has evolved into a major research tool, providing key insights into the relationships between skin, drug and formulation. Sometimes, such studies involve synthetic membranes as this approach can yield useful inferences with respect to drug-skin partitioning and diffusion phenomena. Yet despite the popularity of such studies, it is still not at all known whether typical solute transport across synthetic barriers results in a normal distribution of permeability coefficients or alternatively some type of skewed distribution. The present study aims to shed light on this issue. To this end, five compounds (testosterone, oestradiol, corticosterone, aldosterone and adenosine) exhibiting a broad range of octanol-water partition coefficient values were selected as test penetrants. The protocol involved taking multiple replicate measurements of each drug's passive steady state flux through poly(dimethylsiloxane) membrane. Each penetrant's resultant permeability coefficient database was subjected to a Kolmogorov-Smirnov (KS) test for normality. It was found that the permeability coefficients of all five drugs were distributed in a Gaussian-normal fashion. The theoretical significance and practical impact of these findings are discussed.
在最近几十年里，使用体外扩散池研究来评估皮肤渗透性已发展成为一种主要的研究工具，为深入了解皮肤、药物和制剂之间的关系提供了关键见解。有时，此类研究涉及合成膜，因为这种方法可以就药物与皮肤的分配和扩散现象得出有用的推论。然而，尽管此类研究很受欢迎，但对于典型溶质跨合成屏障的转运是否会导致渗透系数呈正态分布，或者是否会导致某种类型的偏态分布，仍然完全不清楚。本研究旨在阐明这一问题。为此，选择了五种具有广泛辛醇 - 水分配系数值的化合物（睾酮、雌二醇、皮质酮、醛固酮和腺苷）作为测试渗透剂。该方案包括对每种药物通过聚二甲基硅氧烷膜的被动稳态通量进行多次重复测量。对每种渗透剂所得的渗透系数数据库进行柯尔莫哥洛夫 - 斯米尔诺夫（KS）正态性检验。结果发现，所有五种药物的渗透系数均呈高斯正态分布。讨论了这些发现的理论意义和实际影响。
