每克肝脏中人类微粒体蛋白水平和肝细胞数量的个体间变异性。
Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver.
作者信息
Wilson Z E, Rostami-Hodjegan A, Burn J L, Tooley A, Boyle J, Ellis S W, Tucker G T
机构信息
Molecular Pharmacology and Pharmacogenetics, Division of Clinical Sciences (South), The University of Sheffield, Sheffield, UK.
出版信息
Br J Clin Pharmacol. 2003 Oct;56(4):433-40. doi: 10.1046/j.1365-2125.2003.01881.x.
Abstract
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)= 10(7) 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.
摘要
目的
确定每克人肝脏中微粒体蛋白（MPPGL）和肝细胞数量（HPGL）的水平及其个体间变异性。
方法
在考虑处理过程中微粒体蛋白或肝细胞的部分损失后，使用一式三份的肝脏样本确定MPPGL（n = 20）和HPGL（n = 7）的值。对每个肝脏样本进行重复测量，使用方差分析估计MPPGL和HPGL的真实个体间变异性。
结果
MPPGL的值范围为26至54 mg g(-1)（几何平均值 = 33 mg g(-1)）。HPGL的值范围为65至185×10(6)个细胞 g(-1)（几何平均值 = 10(7)×10(6)个细胞 g(-1)）。
结论
MPPGL存在显著的个体间变异性，这对准确外推药物代谢的体外数据以预测体内代谢清除率具有重要意义。
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