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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Hepatocytes / metabolism*
  • Humans
  • Liver / metabolism*
  • Male
  • Microsomes, Liver / metabolism*
  • Middle Aged
  • Proteins / metabolism*

Substances

  • Proteins
  • Cytochrome P-450 Enzyme System