Effects of age and gender on in vitro properties of human liver microsomal monooxygenases.
Aging in humans is associated with marked declines in the disposition of numerous drugs and other xenobiotics that require hepatic biotransformation before elimination. Considerable pharmacokinetic evidence in humans, coupled with data on in vitro liver microsomal monooxygenase functions generated in inbred male rodent models, has implicated impaired liver phase I drug metabolism (i.e., diminished efficacy of microsomal monooxygenases) in reduced drug clearance in the elderly. This study (1) assessed the in vitro activities and amounts of liver microsomal monooxygenases as a function of donor age and gender in healthy humans and (2) provides the most extensive and comprehensive data to date demonstrating the absence of significant age- and gender-dependent differences in the activities and contents of human liver monooxygenases.
Schmucker
D L
DL
Section of Cell Biology, Aging, and Molecular Medicine, Veterans Administration Medical Center, San Francisco, CA 94121.
Woodhouse
K W
KW
Wang
R K
RK
Wynne
H
H
James
O F
OF
McManus
M
M
Kremers
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D002648:Child; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry / Q000201:enzymology*; D008875:Middle Aged; D009251:NADPH-Ferrihemoprotein Reductase / Q000737:chemistry / Q000378:metabolism; D012737:Sex Factors
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase