【作者】 孙进； 隋晓璠； 李海燕； 何仲贵；

【Author】 Jin Sun,Xiaofan Sui,Haiyan Li,Zhonggui He

【机构】 沈阳药科大学药学院生物药剂学研究室；

【摘要】 目的:建立一种准确简便的药物人体稳态分布容积的预测模型,以加快药物候选物的筛选速度,提高药物研发的成功率。方法:用磷脂膜色谱保留因子的对数值和解离分数(fi)、血浆蛋白结合率的对数值建立药物的组织中游离分数的预测模型,进而用φie-Tozer方程计算其人体稳态分布容积。结果:该方法能用于结构各异的化合物,内部和外部验证的结果表明我们的方法预测性好,有着更广的应用范围和更准确的预测能力。结论:建立了一种准确简便的药物人体稳态分布容积的预测模型,有助于缩短新药开发的周期和降低成本。更多还原

【Abstract】 OBJECTIVE To establish an easy,rapid and accurate method to predict VDss values in humans.METHODS Log kIAM,together with fi(7.4)(the fraction of compound ionized at pH 7.4)and log fu(logarithmic the fraction of compound unbound in plasma),the predictive equation of fut(the fraction of the compound unbound in tissues)was built,and the predictive VDss values were further obtained from the ?ie-Tozer equation with the calculated fut and experimental fu values.RESULTS Our model could be applicable to structurally diverse compounds.Interior and exterior validation results indicated the model had a robust predictive ability.And it can be generally applicable with better predictive accuracy.CONCLUSIONS our method is an attractive and promising approach for predicting VDss in human of new candidates in the drug discovery stage.更多还原