期刊
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
卷 56, 期 4, 页码 433-440出版社
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1365-2125.2003.01881.x
关键词
liver microsomes; prediction of metabolic clearance; cytochrome P450; in silico ADME; variability in metabolism
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.
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