Cronin M T, Dearden J C, Moss G P, Murray-Dickson G
School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK.
Eur J Pharm Sci. 1999 Mar;7(4):325-30. doi: 10.1016/s0928-0987(98)00041-4.
Permeability coefficients for 114 compounds across excised human skin in vitro were taken from Kirchner et al. Forty-seven descriptors were calculated encompassing the relevant physicochemical parameters of the compounds. Quantitative structure-permeability relationships (QSPRs) were developed using least-squares regression analysis. A two-parameter QSPR, describing the permeability coefficients (Kp) across excised skin, was obtained: log Kp=0.772 log P -0.0103 Mr - 2.33 where log P is the logarithm of the octanol-water partition coefficient and Mr is molecular mass. This equation indicates that percutaneous absorption is mediated by the hydrophobicity and the molecular size of the penetrant. Comparison with a QSPR based on penetration across a synthetic (polydimethylsiloxane) membrane suggests that the mechanisms of drug flux across polydimethylsiloxane membranes and excised human skin are significantly different.
114种化合物在体外切除的人体皮肤上的渗透系数取自基希纳等人的研究。计算了47个描述符，涵盖了这些化合物的相关物理化学参数。使用最小二乘法回归分析建立了定量结构-渗透关系（QSPR）。得到了一个描述切除皮肤渗透系数（Kp）的双参数QSPR：log Kp = 0.772 log P - 0.0103 Mr - 2.33，其中log P是辛醇-水分配系数的对数，Mr是分子量。该方程表明，经皮吸收由渗透剂的疏水性和分子大小介导。与基于穿过合成（聚二甲基硅氧烷）膜的渗透的QSPR进行比较表明，药物穿过聚二甲基硅氧烷膜和切除的人体皮肤的通量机制显著不同。
