用改进的理论溶剂化方程预测药物的经皮渗透性

Prediction of percutaneous drug permeability using modified theoretical linear solvation energy relationship

目的 :预测药物经过人体表皮的渗透系数。方法 :用半经验自洽场分子轨道 AM1法计算量子化学参数 ,用改进的理论溶剂化方程模型建立药物透过人体表皮的渗透系数的回归方程式。结果 :36个非电解质化合物透过人体表皮的渗透系数 (P)和分子体积 (V)、氢键酸度 (Σα2 H)、氢键碱度 (Σβ2 H)和极化率指数 (πI)等理论参数之间具有良好的线性相关性 ,回归方程式为 :log P=- 6 .790 +1.5 71V+0 .15 5 0 πI- 1.2 95 Σα2 H - 2 .4 85 Σβ2 H (n=36 ,r=0 .9777)。结论 :可以用改进的理论溶剂化方程预测药物的经皮渗透性。

Objective: To predict the percutaneous drug permeability coefficients with modified regression equation.Methods:The semiempirical self-consistent field molecular orbital calculation AM1 method was used to calculate the quantum chemical parameters and the modified theoretical linear solvation energy relationship was used to obtain the regression equation of the permeability coefficients of drugs through human epidermis.Results:The permeability coefficients (P) of 36 nonelectrolytes were well linearly correlated with their theoretical descriptors including molecular volume (V),hydrogen-bond acidity (Σα 2H),hydrogen-bond basicity (Σβ 2H) and polarizability index (π I).The regression equation was logP=-6.790+1.571 V+0.1550 π I-1.295Σα 2H-2.485Σβ 2H(n=36,r=0.9777).Conclusion:The modified theoretical linear solvation energy relationship can be used to predict the skin permeability of drugs.