Cronin M T, Dearden J C, Gupta R, Moss G P
School of Pharmacy and Chemistry, Liverpool John Moores University, UK.
J Pharm Pharmacol. 1998 Feb;50(2):143-52. doi: 10.1111/j.2042-7158.1998.tb06169.x.
Quantitative structure-permeability relationships (QSPRs) based on readily calculated parameters have been developed to study penetration across a polydimethylsiloxane membrane. Maximum steady-state flux values for 256 compounds through a polydimethylsiloxane membrane were taken from previous studies. Forty-three physicochemical parameters were calculated for each compound and their significance to flux determined. Removal of fourteen outliers enabled derivation of a significant three-parameter QSPR based on the number of hydrogen-bond acceptor and donor groups and sixth-order path molecular connectivity. Models based on parameters important for penetration across human skin (log P and molecular weight) were comparatively poor. This model suggests that the mechanism of flux across a polydimethylsiloxane membrane is based mainly on hydrogen-bonding effects; as such it occurs via a mechanism of action different from that of penetration of the skin in man.
基于易于计算的参数建立了定量结构-渗透性相关性（QSPRs），以研究化合物透过聚二甲基硅氧烷膜的渗透情况。先前研究获取了256种化合物透过聚二甲基硅氧烷膜的最大稳态通量值。为每种化合物计算了43个物理化学参数，并确定了它们对通量的重要性。去除14个异常值后，基于氢键受体和供体基团的数量以及六阶路径分子连接性，推导出了一个具有显著意义的三参数QSPR。基于对人体皮肤渗透重要的参数（log P和分子量）建立的模型相对较差。该模型表明，化合物透过聚二甲基硅氧烷膜的通量机制主要基于氢键作用；因此，其作用机制与人体皮肤渗透的机制不同。
