Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver

被引:146
|
作者
Wilson, ZE [1 ]
Rostami-Hodjegan, A [1 ]
Burn, JL [1 ]
Tooley, A [1 ]
Boyle, J [1 ]
Ellis, SW [1 ]
Tucker, GT [1 ]
机构
[1] Univ Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, England
关键词
liver microsomes; prediction of metabolic clearance; cytochrome P450; in silico ADME; variability in metabolism;
D O I
10.1046/j.1365-2125.2003.01881.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims To determine levels of microsomal protein (MPPGL) and hepatocellularity (HPGL) per gram of human liver and their interindividual variability. Methods Triplicate liver samples were used to determine values of MPPGL (n = 20) and HPGL ( n = 7) after accounting for the fractional loss of microsomal protein or hepatocytes during processing. Repeated measurements from each liver sample allowed the estimation of true interindividual variability in MPPGL and HPGL using ANOVA. Results The value of MPPGL ranged from 26 to 54 mg g(-1) (mean(geo) = 33 mg g(-1)). The value of HPGL ranged from 65 to 185 x 10(6) cells g(-1) (mean(geo) = 107 x 10(6) cells g(-1)). Conclusions There is significant interindividual variability in MPPGL, which has implications for the accurate extrapolation of in vitro data on drug metabolism to predict in vivo metabolic clearance.
引用
收藏
页码:433 / 440
页数:8
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