Sex difference in the biliary excretion of digoxin and its metabolites in aging Wistar rats

The biliary excretion of digoxin (Dg3) and its metabolites was studied in both young (3-month-old) and old (25- and 30-month-old) Wistar rats of both sexes. The 2 h biliary recovery (% of the dose) of intravenously injected [3H]Dg3 (0.01 mg/100 g) radioactivity was similar between young male and female rats, while the first 10 min excretion was significantly higher in females. In old (25-month-old) male rats, the 2 h biliary recovery of radioactivity was significantly lower than the corresponding young value. This was primarily due to the drastic decrease with age in excretion of bis-digitoxoside. On the other hand, in old female rats (25- and 30-month-old) the 2 h recovery value was not significantly different from the corresponding young (3-month-old) value. This was due to the much higher percentage (more than 80% of the total) of Dg3 in the female bile radioactivity which did not significantly decrease with age. The results suggest that the rate of stepwise cleavages of the sugar chain of Dg3 decreases with age more rapidly in male than in female rats as has been previously shown by the authors for digitoxin. Large sex differences observed in the age-dependent alteration in Dg3 metabolism and its biliary excretion raise a caution against a generalization of the data obtained from a single sex in this animal species with regard to the effect of aging.