Investigation of the mechanism of flux across human skin in vitro by quantitative structure-permeability relationships
Investigation of the mechanism of flux across human skin in vitro by quantitative structure-permeability relationships
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DOI：
10.1016/s0928-0987(98)00041-4
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发表时间：
1999-03-01
影响因子：
4.6
通讯作者：
Murray-Dickson, G
中科院分区：
文献类型：
--
作者：
Cronin, MTD;Dearden, JC;Murray-Dickson, G
114种化合物在离体人体皮肤中的渗透系数取自Kirchner等人。计算了47个描述符，包括化合物的相关理化参数。定量结构-渗透率关系（QSPR）的开发使用最小二乘回归分析。得到了描述离体皮肤渗透系数（K-p）的双参数QSPR：log K-p = 0.772 log P-0.0103 M-r - 2.33其中log P是辛醇-水分配系数的对数，m是分子质量。该方程表明透皮吸收是由渗透剂的疏水性和分子大小介导的。与QSPR的基础上渗透整个合成（聚二甲基硅氧烷）膜的比较表明，药物通量通过聚二甲基硅氧烷膜和切除的人体皮肤的机制是显着不同的。(C)1999 Elsevier Science B. V.保留所有权利。
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 (K-p) across excised skin, was obtained: log K-p = 0.772 log P -0.0103 M-r - 2.33 where log P is the logarithm of the octanol-water partition coefficient and ill, 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. (C) 1999 Elsevier Science B.V. All rights reserved.