药物分子体积和油水分配系数与经应吸收的关系

以8个对氨基苯甲酸酯化合物为模型药物,测定了它们的辛醇/水分配系数、溶解度及通过大鼠腹部皮肤的渗透速率。用皮肤二层扩散模型,分析药物的经皮渗透系数与分子体积和油水分配系数的关系,导出了以分子体积和油水分配系数预测渗透系数的关系式。药物的渗透系数随分子体积增大而降低。当药物的油水分配系数小时,表现为渗透系数随分配系数的增大而增大;当分配系数大到一定值后,渗透系数不再受分配系数的影响,而随分子体积的增大而减小。

THE EFFECT OF MOLECULAR VOLUME AND PARTITION COEFFICIENT ON PERCUTANEOUS ABSORPTION

A series of 8 p-aminobenzoate esters were selected as model drugs to study the effect of molecular volume and partition coefficient on percutaneous absorption. The octanol/water partition coefficient and solubility of these compounds were determined and their penetration rate through rat skin in vitro was measured using a Keshany-Chien diffusion cell. The results showed that when the molecular volume was increased the permeation coefficient was decreased. However, when the partition coefficient was increased, the permeation coefficient was increased at first and then reached a plateau. The mathematical formula has been derived from a bi-layer diffusion model to show how the molecular volume and the partition coefficient influence the permeation coefficient. The formula could be used to estimate the permeation coefficient of drug through skin.