节点文献
高通量筛选药物的人体稳态分布容积
Prediction of volume of distribution values in human using immobilized artificial membrane partitioning,the ionized fraction of compound and plasma protein binding data
【Author】 SUN Jin,SUI Xiao-fan,LI Hai-yan,HE Zhong-gui Laboratory of Biological Pharmacy,Pharmacy Faculty of Shenyarg Pharmaceutical University,Sheryang 110016,Liaoning,China
【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(f_i)、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。
【Abstract】 AIM: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 di- verse compounds.Interior and exterior validation results indicated the model had a robust predictive ability.And it can be generally applicable with better predictive accuracy.CONCLUSION:Our method is an attractive and promising approach for predicting VDss in human of new candidates in the drug discovery stage.
【Key words】 Volume of distribution； immobilized artificial membrane chromatography； plasma protein binding；
- 【会议录名称】 第九届全国药物和化学异物代谢学术会议论文集
- 【会议名称】第九届全国药物和化学异物代谢学术会议
- 【会议时间】2009-10-23
- 【会议地点】中国湖北武汉
- 【分类号】R96
- 【主办单位】中国药理学会药物代谢专业委员会