Kobayashi Yoichi, Komatsu Tsunehisa, Sumi Machiko, Numajiri Sachihiko, Miyamoto Misao, Kobayashi Daisuke, Sugibayashi Kenji, Morimoto Yasunori
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
Eur J Pharm Sci. 2004 Mar;21(4):471-7. doi: 10.1016/j.ejps.2003.11.008.
The objectives of the present study are to clarify the relationship between the physicochemical properties and the nail permeability of drugs through human nail plates. Homologous p-hydroxybenzoic acid esters were used to investigate the relationship between the octanol/water partition coefficient and the permeability coefficient of several drugs. The nail permeability was found to be independent of the lipophilicity of a penetrating drug. However, the nail permeability of several model drugs was found to markedly decrease as their molecular weights increased. The nail permeability of an ionic drug was found to be significantly lower than that of a non-ionic drug, and the nail permeability of these drugs markedly decreased as their molecular weights increased. The permeation of a model drug, 5-fluorouracil (5-FU), through healthy nail plates was also determined and compared with that through nail plates with fungal infections. The drug permeation through a nail plate decreased with an increase in nail plate thickness. Nail plates with fungal infections exhibited approximately the same 5-FU permeation as healthy nail plates. We suggest that the permeability of a drug is mainly influenced by its molecular weight and permeability through nails with fungal infection can be estimated from data on healthy nail permeability.
本研究的目的是阐明药物的理化性质与通过人体指甲板的透性之间的关系。使用同系对羟基苯甲酸酯来研究几种药物的正辛醇/水分配系数与渗透系数之间的关系。发现指甲透性与渗透药物的亲脂性无关。然而，发现几种模型药物的指甲透性随着其分子量的增加而显著降低。发现离子型药物的指甲透性明显低于非离子型药物，并且这些药物的指甲透性随着其分子量的增加而显著降低。还测定了模型药物5-氟尿嘧啶（5-FU）通过健康指甲板的渗透，并与通过真菌感染指甲板的渗透进行了比较。药物通过指甲板的渗透随着指甲板厚度的增加而降低。真菌感染的指甲板表现出与健康指甲板大致相同的5-FU渗透性。我们认为，药物的渗透性主要受其分子量影响，并且可以根据健康指甲渗透性的数据来估计药物在感染真菌的指甲中的渗透性。
