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目的利用QSPR模型预测药物的经皮渗透性,并检验模型的准确性和适用性。方法以炔雌醇、α-细辛醚、非那甾胺和利培酮为模型药物,Potts-Guy,Cronin,Moss,Morrimoto,Kitagawa,Magnusson和Lien-Gao构建的七个数学等式为QSPR模型,用药物的理化参数计算药物经皮渗透速率的预测值;同时采用离体人皮,在透皮扩散池中进行饱和药物溶液的体外经皮渗透实验。高效液相色谱法测定接受液中的药物浓度,计算药物的最大稳态经皮渗透速率。并将利用模型得到的理论预测值与实验所得的实际经皮渗透数值进行比较和分析,确定最适预测模型。结果采用7种预测模型所得到的理论预测值相对于实验值均在95%可信区间内,具有统计学意义。模型之间的准确度有很大差异,采用疏水性和相对分子质量为参数的模型拟合效果最好,根据均方根误差RMSE(Root Mean Square of Error),预测的准确性程度依次为Potts-Guy>Cronin>Kitagawa,Morimoto,Magnusson>Moss,Lien-Gao。结论QSPR模型能很好地预测药物的经皮渗透,Potts-Guy预测的准确性最佳。
Objective To predict the transdermal permeability of drug using QSPR model and test the accuracy and applicability of the model. Methods Seven mathematical equations constructed by Potts-Guy, Cronin, Moss, Morrimoto, Kitagawa, Magnusson and Lien-Gao using ethinylestradiol, alpha-asarone, finasteride and risperidone as model drugs were QSPR Model, the physical and chemical parameters of the drug were used to calculate the predictive value of the transdermal penetration rate of the drug. In vitro transdermal permeation experiments of saturated drug solution were carried out in the transdermal diffusion cell with ex vivo human skin. The drug concentration in the receiving fluid was determined by high performance liquid chromatography, and the maximum steady-state transdermal permeation rate of the drug was calculated. The theoretical predictive value obtained by the model is compared with the actual transdermal permeation value obtained from the experiment to determine the optimal predictive model. Results The theoretical predictions obtained from the seven prediction models were all within 95% confidence intervals with respect to the experimental values, with statistical significance. The accuracy of the model is very different. The model with the hydrophobicity and the relative molecular mass as the parameters has the best fitting effect. According to Root Mean Square of Error (RMSE), the accuracy of prediction is Potts -Guy> Cronin> Kitagawa, Morimoto, Magnusson> Moss, Lien-Gao. Conclusion The QSPR model can predict the transdermal penetration of drug well and the accuracy of Potts-Guy prediction is the best.