Pharmacokinetics of tritiated ouabain, digoxin and digitoxin in guinea‐pigs

Abstract

1. Elimination rates of tritiated ouabain, digoxin and digitoxin after single intravenous administrations were investigated in guinea-pigs, the total radioactivity in whole blood being traced for a period of up to 2 weeks. 2. In the initial rapid phase of elimination between 2 and 30 min following intravenous glycoside administration, the concentration decline of radioactivity in the blood was found to be identical for the three glycosides investigated, this part of the elimination curve displaying a hyperbolic shape. 3. During this early elimination phase, rapid metabolic degradation and excretion of digoxin had already taken place. The maximum concentration of radioactivity in the bile was reached 4 min following intravenous administration of 3H-digoxin. The positive inotropic response occurred in the cat heart-lung preparation 1.5 min after intravenous injection of a therapeutic dose of digoxin, indicating a quick occupation of binding sites in the tissues. 4. The biological half-lives of tritiated ouabain, digoxin and digitoxin averaged 11 h, 2.5 days and 4.1 days, respectively, as determined by the terminal exponential elimination phase, in guinea-pigs. This terminal phase was attained 6-12, 7-24, and 24-48 h after administration of ouabain, digoxin and digitoxin, respectively. 5. The findings reveal that in guinea-pig, as has been demonstrated in man, the elimination rates of the three glycosides increase according to their hydrophobic properties. 6. The biological half-lives of tritiated ouabain, digoxin and digitoxin obtained in the guinea-pig closely resemble those found in healthy man.

Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease

“…Ouabain secretion is also stimulated by ACTH, angiotensin II (ANG II), and ␣1-adrenergic receptor agonists (179). Data on other characteristics of endogenous ouabain, such as its half-life in plasma, metabolism, and elimination, are scarce and mostly limited to the pharmacokinetic and pharmacodynamic information reported for exogenously administered ouabain (92,169,182,183).…”