Age-Related Pharmacokinetics of Ouabain in Rats 1

Abstract

Abstract

The pharmacokinetics of ouabain was studied in 2- and 6-month-old rats in an attempt to determine the factors responsible for the marked difference in the plasma disappearance of ouabain from rats of these two ages. Biliary excretion of the two groups was also compared. Plasma concentration of ouabain in older rats was significantly higher than that of the young rats. The plasma concentration data for both groups were fitted to the triexponential equation C₁ = Pe^πt + Ae^αt + Be^βt . A significant increase was observed in both B and the area under the plasma concentration verses time curve (AUC) in the older rats, while significant decreases were observed in the mean plasma clearance and volume of distribution. The slope of the terminal phase (β) was similar in both groups. No significant difference was observed in the cumulative biliary excretion or the biliary excretory rate. The age-associated difference in plasma elimination of ouabain appears to be due to a difference in volume of distribution rather than decreased biliary excretion of ouabain.