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

来源：

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY | 2003年 / 56卷 / 04期

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

页码：433 / 440

页数：8

共 50 条

[31] Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome
Illingworth, Robert S.
Gruenewald-Schneider, Ulrike
De Sousa, Dina
Webb, Shaun
Merusi, Cara
Kerr, Alastair R. W.
James, Keith D.
Smith, Colin
Walker, Robert
Andrews, Robert
Bird, Adrian P.
NUCLEIC ACIDS RESEARCH, 2015, 43 (02) : 732 - 744
[32] Nonsense-mediated mRNA decay: Inter-individual variability and human disease
Lam Son Nguyen
Wilkinson, Miles F.
Gecz, Jozef
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 2014, 46 : 175 - 186
[33] The widespread increase in inter-individual variability of gene expression in the human brain with age
Kedlian, Veronika R.
Donertas, Handan Melike
Thornton, Janet M.
AGING-US, 2019, 11 (08): : 2253 - 2280
[34] A study of inter-individual variability in the Phase II metabolism of xenobiotics in human skin
Spriggs, Sandrine
Cubberley, Richard
Loadman, Paul
Sheffield, David
Wierzbicki, Antonia
TOXICOLOGY LETTERS, 2018, 292 : 63 - 72
[35] Anatomy of human sensory cortices reflects inter-individual variability in time estimation
Gilaie-Dotan, Sharon
Kanai, Ryota
Rees, Geraint
FRONTIERS IN INTEGRATIVE NEUROSCIENCE, 2011, 5
[36] Geographic differences in inter-individual variability of human exposure to fine particulate matter
Cao, Ye
Frey, H. Christopher
ATMOSPHERIC ENVIRONMENT, 2011, 45 (32) : 5684 - 5691
[37] Assessment of inter-individual variability in predicted phenytoin clearance
Thomas M. Polasek
Sebastian Polak
Matthew P. Doogue
Amin Rostami-Hodjegan
John O. Miners
European Journal of Clinical Pharmacology, 2009, 65 : 1203 - 1210
[38] Inter-individual variability of calorie restriction responses in humans
Redman, L. M.
Ravussin, E.
EXPERIMENTAL GERONTOLOGY, 2009, 44 (1-2) : 131 - 132
[39] Overview of the role for studies of inter-individual variability in toxicology
McAllister, K.
TOXICOLOGY LETTERS, 2022, 368 : S6 - S7
[40] Inter-individual variability in the catalytic activity of CYP3A4 per unit of enzyme (kcat)
Lei, Y
Wilson, ZE
Crewe, KH
Tucker, GT
Rostami-Hodjegan, A
DRUG METABOLISM REVIEWS, 2005, 37 : 54 - 54

← 1 2 3 4 5 →