Biliary excretion of digitoxin and its metabolites in young and old male Wistar rats.
The biliary excretion of digitoxin (Dt3) and its metabolites were compared between young (3-month-old) and old (25-month-old) male Wistar rats after an iv injection of [3H]Dt3 (0.03 mg/100g body weight) for 2 hrs. The 2-hr. total biliary recovery of iv injected radioactivity (percent of the dose) was two times lower in old rats (7.40 +/- 1.36% mean +/- SD) compared with young rats (14.74 +/- 4.10%). This difference was primarily due to the decrease in the excretion of Dt3 metabolites in the bile, while the excretion of the parent drug, Dt3 was 1.3 times higher in old rats. Among various Dt3 metabolites in the bile, digitoxigenin bis-digitoxoside (Dt2), digoxigen bis-digitoxoside (Dg2), and polar (conjugated) metabolites were major components, which all decreased with age. In accord with the decreased excretion of the radioactivity in the bile of old rats, the plasma disappearance of radioactivity was generally slower in old animals compared with young ones, yielding significantly higher plasma levels at different times of observation. Despite the increase in plasma radioactivity, the radioactivity concentration in the liver 2 hrs. after the injection was almost equal between the two age groups. It is suggested that at least in this rat strain and sex the biliary excretion of Dt3 metabolites was markedly age-dependent, presumably due to the decreased capacity of the liver to biotransform Dt3 with age. Furthermore, the lower liver plasma radioactivity ratio in old animals suggested the possibility that the distribution of Dt3 in the liver may also decrease with age.
D000375:Aging; D000818:Animals; D001646:Bile / Q000378:metabolism*; D004073:Digitoxigenin / Q000031:analogs & derivatives / Q000378:metabolism; D004074:Digitoxin / Q000097:blood / Q000378:metabolism*; D004076:Digoxigenin / Q000031:analogs & derivatives / Q000378:metabolism; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004073:Digitoxigenin; C038148:digitoxigenin-bis(digitoxoside); C023685:digoxigenin-bis(digitoxoside); D004074:Digitoxin; D004076:Digoxigenin