Ottaviani Giorgio, Martel Sophie, Carrupt Pierre-Alain
LCT-Pharmacochimie, Section des Sciences Pharmaceutiques, Université de Genève, Quai Ernest-Ansermet 30, CH-1211, Genève 4, Switzerland.
J Med Chem. 2006 Jun 29;49(13):3948-54. doi: 10.1021/jm060230+.
This work was devoted to the search for new artificial membranes allowing a rapid evaluation of passive human skin permeation of compounds with a parallel artificial membrane permeability assay (PAMPA). Effective permeability coefficients (Pe) determined for a set of compounds using the PAMPA technique with isopropyl myristate (IPM) and silicone oil, alone or in mixture, were compared to the corresponding human skin permeability coefficient values (Kp). A good correlation between Pe and Kp was found for compounds tested through a membrane consisting of 70% silicone and 30% IPM. Moreover, positive correlation between the membrane retention of compounds and stratum corneum/water partition coefficients (PSC) was established. These results showed that this new artificial membrane, defined as PAMPA-skin, is able to mimic the main barrier properties of human stratum corneum and can be used for the fast prediction of passive human skin permeability coefficients.
这项工作致力于寻找新型人工膜，以便通过平行人工膜通透性测定法（PAMPA）快速评估化合物在人体皮肤中的被动渗透情况。使用含有肉豆蔻酸异丙酯（IPM）和硅油单独或混合的PAMPA技术，测定了一组化合物的有效渗透系数（Pe），并将其与相应的人体皮肤渗透系数值（Kp）进行比较。对于通过由70%硅油和30% IPM组成的膜测试的化合物，发现Pe与Kp之间具有良好的相关性。此外，还建立了化合物在膜上的保留率与角质层/水分配系数（PSC）之间的正相关关系。这些结果表明，这种定义为PAMPA-皮肤的新型人工膜能够模拟人体角质层的主要屏障特性，可用于快速预测化合物在人体皮肤中的被动渗透系数。
