The effect of age on digoxin pharmacokinetics in Fischer-344 rats

• Published in: Toxicology and applied pharmacology Vol. 102; no. 1; p. 61
• Main Authors: Evans, R L, Owens, S M, Ruch, S, Kennedy, R H, Seifen, E
• Format: Journal Article
• Language: English
• Published: United States 01.01.1990
• Subjects: Aging - drug effects; Aging - metabolism; Animals; Blood Proteins - drug effects; Blood Proteins - metabolism; Chromatography, High Pressure Liquid - methods; Digoxin - blood; Digoxin - pharmacokinetics; Injections, Intravenous; Male; Protein Binding - drug effects; Rats; Rats, Inbred F344 - metabolism; Rats, Inbred Strains - metabolism; Tritium
• ISSN: 0041-008X
• DOI: 10.1016/0041-008x(90)90083-7

Digoxin protein binding and pharmacokinetics were studied in 4-, 14-, and 25-month-old male Fischer-344 rats to determine if there were age-dependent changes in digoxin disposition. Serum protein binding did not differ among age groups. The average percentage unbound digoxin for all animals was 61.3 +/- 5.3% (means +/- SD, n = 15). For pharmacokinetic studies, [3H]digoxin and 1 mg/kg unlabeled digoxin were administered as an intravenous bolus dose to animals from each age group. The [3H]digoxin terminal elimination half-life was 2.0, 2.3, and 2.5 hr, respectively. The steady-state volume of distribution in the three age groups was 1.51, 1.49, and 1.27 liters/kg, respectively. Total body clearance for the three age groups was 14.2, 12.1, and 7.5 ml/min/kg, respectively. Analysis of variance of these data followed by Duncan's multiple range test indicated a significant decrease in clearance in the aged rats (25-month-old, p less than 0.05). This age-dependent decrease in clearance suggested that digoxin pharmacokinetics could be a significant factor in age-related alterations in digoxin cardiotoxicity in the rat, as it is in humans, and that the Fischer-344 rat could be a useful model for studies of digoxin pharmacokinetic changes with age.