Content and activity of human liver microsomal protein and prediction of individual hepatic clearance in vivo.
Content and activity of human liver microsomal protein and prediction of individual hepatic clearance in vivo.
复制标题
人肝微粒体蛋白含量、活性及体内个体肝清除率预测
DOI：
10.1038/srep17671
复制
发表时间：
2015-12-04
影响因子：
4.6
通讯作者：
Qiao H
中科院分区：
文献类型：
--
作者：
Zhang H;Gao N;Tian X;Liu T;Fang Y;Zhou J;Wen Q;Xu B;Qi B;Gao J;Li H;Jia L;Qiao H
The lack of information concerning individual variation in content and activity of human liver microsomal protein is one of the most important obstacles for designing personalized medicines. We demonstrated that the mean value of microsomal protein per gram of liver (MPPGL) was 39.46 mg/g in 128 human livers and up to 19-fold individual variations existed. Meanwhile, the metabolic activities of 10 cytochrome P450 (CYPs) were detected in microsomes and liver tissues, respectively, which showed huge individual variations (200-fold). Compared with microsomes, the activities of liver tissues were much suitable to express the individual variations of CYP activities. Furthermore, individual variations in the in vivo clearance of tolbutamide were successfully predicted with the individual parameter values. In conclusion, we offer the values for MPPGL contents in normal liver tissues and build a new method to assess the in vitro CYP activities. In addition, large individual variations exist in predicted hepatic clearance of tolbutamide. These findings provide important physiological parameters for physiologically-based pharmacokinetics models and thus, establish a solid foundation for future development of personalized medicines.
