Institute of Clinical Pharmacy and Pharmaceutical Sciences, Tainan, Taiwan, ROC.
Skin Pharmacol Physiol. 2012;25(3):124-32. doi: 10.1159/000336245. Epub 2012 Feb 15.
The objective of this study was to investigate the effect of sebum on drug transport across the human stratum corneum (SC) in vivo for two model compounds, 4-cyanophenol (CP) and cimetidine (CM), of different lipophilicity and molecular size by utilizing noninvasive tape-stripping techniques, in conjunction with an unsteady-state diffusion model for data analysis. The results demonstrated that the SC permeability of the relatively hydrophilic CM on the forehead may be as much as four times the permeability on the forearm. The administration of sebum supplementation to the forearm increased the SC permeability of CM more than threefold, but did not have the same effect with regard to CP. Removal of sebum from the forehead demonstrated a small but significant effect (-22%) on the SC permeability of CM. The presence of sebum on the forehead or forearm increased the diffusion of both molecules, but the effect on partition varied between sites and drugs. The change in the SC permeability of the relatively hydrophilic drug using sebum treatment may be attributable to the altered barrier function of the SC due to the disordering structures of the intercellular lipid molecules.
本研究旨在通过非侵入性的胶带剥离技术，结合非稳态扩散模型进行数据分析，研究皮脂对两种不同亲脂性和分子大小的模型化合物（4-氰苯酚[CP]和西咪替丁[CM]）在人体角质层（SC）中体内药物传输的影响。结果表明，相对亲水的 CM 在额部的 SC 渗透性可能是在前臂的四倍。皮脂补充剂在前臂的给药使 CM 的 SC 渗透性增加了三倍以上，但对 CP 没有相同的影响。从额头上除去皮脂对 CM 的 SC 渗透性有一个小但显著的影响（-22%）。皮脂存在于额头或前臂会增加两种分子的扩散，但对不同部位和药物的分配有影响。使用皮脂处理后相对亲水药物的 SC 渗透性的变化可能归因于由于细胞间脂质分子的无序结构，SC 的屏障功能发生改变。
