Pharmacokinetics, bioavailability, and dosage regimens of digoxin in dogs

Digoxin, 30 micrograms/kg, was given by IV injection and orally, in the forms of pediatric elixir and tablet, on three separate occasions to six healthy dogs. Multiple serum samples were collected at timed intervals and assayed by radioimmunoassay. Data were analyzed, using nonlinear least squares regression analysis. The mean serum digoxin-time relationship was triexponential. Rapid and slow distributive phases with half lives of 9 minutes and 4.7 hours were followed by a biological disposition phase with a half life of 30.1 hours. Mean volume of distribution by extrapolation was 15.6 L/kg. When calculated by the area method, mean volume of distribution was 12.4 L/kg. Digoxin elixir was rapidly absorbed, with a mean bioavailability estimate of 71.4 +/- 8.2% SD. Digoxin tablets were less rapidly and less completely absorbed, with a mean bioavailability estimate of 58.0 +/- 11.6%. Data collected in this series of experiments and data from the literature were applied to standard pharmacokinetic equations to formulate loading and maintenance doses of digoxin for the IV injection, the elixir, and the tablet. Mean loading doses were, in micrograms/kg/24 hours: 27, 38, and 45 for the IV injection, elixir, and tablet, respectively. Corresponding mean maintenance doses were 13, 18, and 23.