title: Content and activity of human liver microsomal protein and prediction of individual hepatic clearance in vivo.
abstract: 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.
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Qi
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Hongmeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Linjing
authors.initials: L
authors.lastname: Jia
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China.
authors.forename: Hailing
authors.initials: H
authors.lastname: Qiao
mesh_terms: D000328:Adult; D000368:Aged; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics*; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism*; D008875:Middle Aged; D057285:Precision Medicine
chemical_list: D003577:Cytochrome P-450 Enzyme System