The effect of age on the biliary excretion of digitoxin and its metabolites in female BN/Bi rats.

The biliary excretion of digitoxin (Dt3) and its metabolites was studied in female BN/Bi rats of different ages ranging from 3 to 30 mth. The disappearance of radioactivity from plasma after an i.v. injection of [3H]Dt3 (0.01 mg/100 g body weight) gradually slowed as rat age advanced. The 2-h biliary recovery of radioactivity (percent of the dose) also showed an age-dependent decrease resulting in a 43% decrease at 30 mth compared to the 3-mth-old value. The amount of unchanged Dt3 in the bile, which was about 20% of the total activity in the bile of 3-mth-old rats, did not decrease with age, while the excretion of various Dt3 metabolites all decreased with age. It is suggested that the capacity of the liver to metabolize Dt3 is decreased with age in female BN/Bi rats, which may cause an alteration in the Dt3 pharmacokinetics with age.