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
相关论文
共 50 条
  • [21] Understanding and Managing INTER-Individual Pharmacokinetic Variability
    Baker, S.
    EUROPEAN JOURNAL OF CANCER, 2012, 48 : 73 - 73
  • [22] Microsomal protein per gram of liver (MPPGL) in paediatric biliary atresia patients
    De Bock, Lies
    Boussery, Koen
    De Bruyne, Ruth
    Van Winckel, Myriam
    Stephenne, Xavier
    Sokal, Etienne
    Van Bocxlaer, Jan
    BIOPHARMACEUTICS & DRUG DISPOSITION, 2014, 35 (05) : 308 - 312
  • [23] Inter-individual variability in response of mice to cylindrospermopsin
    Norris, R
    Seawright, A
    Shaw, G
    Moore, M
    TOXICOLOGY, 2001, 164 (1-3) : 184 - 184
  • [24] Issues in predicting inter-individual variability of pharmacokinetics
    Hisaka, Akihiro
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2011, 115 : 19P - 19P
  • [25] Inter-individual differences in heart rate variability are associated with inter-individual differences in mind-reading
    Alexander Lischke
    Daniela Lemke
    Jörg Neubert
    Alfons O. Hamm
    Martin Lotze
    Scientific Reports, 7
  • [26] Inter-individual differences in heart rate variability are associated with inter-individual differences in mind-reading
    Lischke, Alexander
    Lemke, Daniela
    Neubert, Joerg
    Hamm, Alfons O.
    Lotze, Martin
    SCIENTIFIC REPORTS, 2017, 7
  • [27] Intra- and Inter-individual Variability of microRNA Levels in Human Cerebrospinal Fluid: Critical Implications for Biomarker Discovery
    Hyejin Yoon
    Krystal C. Belmonte
    Tom Kasten
    Randall Bateman
    Jungsu Kim
    Scientific Reports, 7
  • [28] Intra- and Inter-individual Variability of microRNA Levels in Human Cerebrospinal Fluid: Critical Implications for Biomarker Discovery
    Yoon, Hyejin
    Belmonte, Krystal C.
    Kasten, Tom
    Bateman, Randall
    Kim, Jungsu
    SCIENTIFIC REPORTS, 2017, 7
  • [29] Anatomy of human sensory cortices reflects inter-individual variability in time estimation
    Gilaie-Dotan, S.
    Kanai, R.
    Rees, G.
    JOURNAL OF MOLECULAR NEUROSCIENCE, 2012, 48 : S57 - S57
  • [30] Inter-individual variability of the aryl hydrocarbon receptor (AHR) in two human populations
    Wong, JMY
    Harper, PA
    Okey, AB
    FASEB JOURNAL, 1997, 11 (09): : A822 - A822