Abstract：
Membrane permeability is one of the main determinants for the absorption, distribution, metabolism and excretion of compounds and is therefore of crucial importance for successful drug development. Experiments with artificial phospholipid membranes have shown that the intrinsic membrane permeability (P0) of compounds is well-predicted by the solubility-diffusion model (SDM). However, using the solubility-diffusion model to predict the P0 of biological Caco-2 and MDCK cell membranes has proven unreliable so far. Recent publications revealed that many published P0 extracted from Caco-2 and MDCK experiments are incorrect. In this work, we therefore used a small self-generated set as well as a large revised set of experimental Caco-2 and MDCK data from literature to compare experimental and predicted P0. The P0 extracted from Caco-2 and MDCK experiments were systematically lower than the P0 predicted by the solubility-diffusion model. However, using the following correlation: log P0,Caco-2/MDCK = 0.84 log P0,SDM - 1.85, P0 of biological Caco-2 and MDCK cell membranes was well-predicted by the solubility-diffusion model.
摘要：
膜的渗透性是决定吸收的主要因素之一,分布，化合物的代谢和排泄，因此对成功的药物开发至关重要。人工磷脂膜的实验表明，化合物的固有膜通透性（P0）可以通过溶解度-扩散模型（SDM）很好地预测。然而,到目前为止，使用溶解度-扩散模型来预测生物Caco-2和MDCK细胞膜的P0已被证明是不可靠的。最近的出版物揭示了许多公开的从Caco-2和MDCK实验中提取的P0是不正确的。在这项工作中,因此,我们使用了一个小的自生成集以及一个大的修改后的实验Caco-2和文献中的MDCK数据来比较实验和预测的P0.从Caco-2和MDCK实验中提取的P0系统地低于溶解度-扩散模型预测的P0。然而,使用以下相关性：logP0，Caco-2/MDCK=0.84logP0，SDM-1.85，生物Caco-2和MDCK细胞膜的P0通过溶解度-扩散模型很好地预测。
