Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver.
OBJECTIVE
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.
Wilson
Z E
ZE
Molecular Pharmacology and Pharmacogenetics, Division of Clinical Sciences (South), The University of Sheffield, Sheffield, UK.
Rostami-Hodjegan
A
A
Burn
J L
JL
Tooley
A
A
Boyle
J
J
Ellis
S W
SW
Tucker
G T
GT
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*
D011506:Proteins; D003577:Cytochrome P-450 Enzyme System