Bergström Christel A S
Center of Pharmaceutical Informatics, Department of Pharmacy, Uppsala University, BMC, P.O. Box 580, SE-751 23 Uppsala, Sweden.
Basic Clin Pharmacol Toxicol. 2005 Mar;96(3):156-61. doi: 10.1111/j.1742-7843.2005.pto960303.x.
Aqueous drug solubility and intestinal drug permeability are two of the most important factors influencing drug absorption. If the developability of a drug is to be included in the lead optimization, new experimental and computational models of solubility and permeability are needed. These models must have the capacity to handle a large amount of data. Nowadays, epithelial cell culture models such as Caco-2 are routinely used to assess intestinal drug permeability and transport in drug discovery settings. The permeability values obtained from the Caco-2 cell monolayers have been traditionally used to devise in silico models for the prediction of drug absorption. In this paper, the use of molecular surface areas as descriptors of permeability and solubility will be reviewed. Moreover, a virtual filter for the prediction of oral drug developability based on the successful combination of in vitro and in silico models of drug permeability and aqueous drug solubility will be discussed.
药物的水溶解度和肠道药物渗透性是影响药物吸收的两个最重要因素。如果要在先导化合物优化中考虑药物的可开发性，就需要新的溶解度和渗透性实验及计算模型。这些模型必须具备处理大量数据的能力。如今，在药物研发环境中，诸如Caco-2等上皮细胞培养模型常被用于评估肠道药物渗透性和转运。从Caco-2细胞单层获得的渗透性值传统上被用于设计计算机模拟模型以预测药物吸收。本文将综述使用分子表面积作为渗透性和溶解度描述符的情况。此外，还将讨论一种基于药物渗透性和水溶解度的体外和计算机模拟模型成功结合来预测口服药物可开发性的虚拟筛选方法。
