介绍一种新型的药物分配和吸收机制的定量评价方法:线性溶剂化能量方程法

A new method for quantitative assessment of mechanisms of partitioning and absorption of drugs: linear solvation energy relationships

线性溶剂化能量方程是研究药物定量结构-保留/活性关系、预测色谱系统中药物保留指数的重要工具。根据线性溶剂化方程建立了生物膜多种体外模拟模型中药物保留因子与其分子描述符之间的定量关系,以及阐明药物-膜作用机制。此外,根据线性溶剂化方程建立了定量结构-活性关系用于预测药物肠吸收、血脑屏障通透性和皮肤透过性。本文综述了线性溶剂化能量方程在定量评价药物分配机制和吸收方面的重要意义及其广泛应用,并指出了该方程的局限性,为研究药物分配和吸收提供新思路。

Linear solvation energy relationships are of a great value in investigating quantitative structure-retention relationship and quantitative structure-activity relationship, and predicting chromatographic retention indices of drugs. Several quantitative relationships in different in vitro biomembrane-mimetic models between retention factors and molecular descriptors have been established successfully and used to clarify drug-membrane interaction mechanisms. Quantitative structure-activity relationships also have been established to predict drug intestinal absorption, permeation of skin and bloodbrain barrier. This review focused on the significance and widely application of linear solvation energy relationships in quantitative assessment for mechanisms of partitioning and absorption of drugs. The discrepancy and limits of linear solvation energy relationships were also discussed, which gives us a better insight into investigation of partitioning and absorption of drugs.