The effect of aging on hepatic
drug conjugation in 5- to 6-, 12- to 13- and 22- to 23-month-old female Fischer 344 rats was examined. The overall disposition of
acetaminophen including the formation and elimination kinetics of its
sulfate and
glucuronide metabolites were used as in vivo probes. The effects of aging on selected in vitro
drug metabolizing
enzyme activities and on the pattern of
phenol and
bile salt sulfotransferase isoenzymes were also determined. Aging decreased the total clearance of
acetaminophen and the partial clearance of
acetaminophen to
acetaminophen sulfate by 36 and 47%, respectively. Increasing age also resulted in a reduced partial clearance of
acetaminophen to the
glucuronide- (24%) and to the
glutathione-derived conjugates (29%).
UDP glucuronosyltransferase activity toward
1-naphthol,
morphine and
testosterone was unaffected by advanced age, whereas there was a significant correlation between increased age and increased
UDP glucuronosyltransferase activity toward
estrone.
Cytochrome P-450 concentration and
glutathione-S-transferase activity toward
1-chloro-2,4-dinitrobenzene were unchanged by aging. Oxidative demethylase activity toward
p-nitroanisole was decreased 18% and
sulfotransferase activities toward
p-nitrophenol,
acetaminophen and
glycolithocholate were decreased 27, 12 and 12%, respectively, in the 22- to 23-month-old rats, compared to the 5- to 6-month-old animals. In contrast to the age-related
feminization in the pattern of
sulfotransferase isoenzyme activities that occurs in male rats, there was no effect of aging on the pattern of
phenol and
bile salt sulfotransferase isoenzyme activities in female rats.(ABSTRACT TRUNCATED AT 250 WORDS)