Plasma Concentrations of Digoxin and Digitoxin During Digitalization of Healthy Dogs and Dogs with Cardiac Failure

SUMMARY Digitalization with digoxin, applying the principle of loading until toxicosis appears, resulted in high plasma concentrations (2.6 to 7.6 ng/ml) in healthy dogs as well as in dogs with cardiac failure. Loading the same dogs with approximately half these doses was sufficient to obtain plasma concentrations from 1.5 to 2.5 ng/ml but avoiding toxicosis. Maintenance doses of digoxin of approximately 0.01 mg/ kg of body weight/12 hours gave plasma concentrations that were over 2.0 ng/ml in some healthy animals and lower than 1.0 ng/ml in others. The mean half-life of digoxin in healthy animals was 31.3 hours. The loading dose of digitoxin resulted in maximal plasma concentrations varying considerably from animal to animal (26 to 77 ng/ml). An interruption of dosing with digitoxin for 24 hours resulted in an almost complete elimination of the drug in most dogs. This is consistent with the short half-life of digitoxin calculated during the first 30 hours after administration of the dose (mean value 13.1 hours). If therapeutic concentrations accepted in man were applied to dogs, a maintenance dose of 0.03 mg/kg of body weight/12 hour of digitoxin elixir resulted in low plasma values (<15 ng/ml) in 5 of the 8 healthy dogs. In 5 of the 6 dogs with cardiac failure, digoxin maintenance doses of 0.007 to 0.010 mg/kg/12 hour gave rise to plasma concentrations ranging from 0.8 to 1.9 ng/ml and were accompanied by clinical improvement. In 1 dog, improvement was not seen although plasma concentrations were as high as 3.0 ng/ml. It is concluded that large loading doses of digoxin are not needed to obtain (within 48 hours) plasma concentrations of the same range as those obtained during maintenance therapy. On the other hand, the often recommended guideline maintenance dose of 0.02 mg/kg/day for digoxin seems a reasonable average, but the recommended maintenance dose of 0.06 mg/kg/day for digitoxin elixir results in low plasma values.