1986 Volume 1 Issue 2 Pages 161-170
The influence of age and sex on the metabolism of tiaramide was studied in young (1 month), young-adult (2 months), middle-aged (12 months) and old (24 months) rats. Formation of the N-dealkylated metabolite by hepatic microsomes was highest in the young-adult males and decreased with aging. In the females, the formation was also maximal in the young-adults, became minimum in the middle-aged and reached the intermediate level in the old. Formation of the N-oxide metabolite by the microsomes was highest in the young-adult and middle-aged males and decreased with aging. In the females, the formation was low in the young-adults, increased to maximum in the middle-aged and decreased slightly from the maximal level in the old. The formation of two metabolites by the microsomes was higher in the young-adult and middle-aged males than in the corresponding females. Formation of tiaramide O-sulfate by hepatic 105, 000 g supernatants was maximal in the young males, decreased markedly in the young-adult and middle-aged males and increased again to the intermediate level in the old males. In the females, the sulfate formation by the supernatants was highest in the young-adults, decreased to minimum in the middle-aged, which was similar to the young, and increased again to the intermediate level in the old. The formation by the supernatants was higher in all females than males. Changes in urinary excretion of the metabolites exhibited age- and sex-related changes nearly similar to the formation by the rat liver. These results suggest that age- and sex-related changes in the hepatic metabolism of tiaramide reflect the changes in the urinary excretion of the metabolites in rats.
