Effects of compensated heart failure on digoxin pharmacokinetics in cats
Authors: Atkins Clarke E. , Snyder Patti S. , Keene Bruce W. , Rush John E. 
Published: February 2025

To evaluate the effects of compensated heart failure (hf) on digoxin pharmacokinetic properties in cats, 6 cats with dilated cardiomyopathy were compared with 6 clinically normal (control) cats. Digoxin tablets were administered at a dosage of 0.01 mg/kg of body weight, q 48 h for approximately 10 days, until presumed steady state was reached. Both groups were treated concomitantly with aspirin, furosemide, and a commercial low-salt diet. Retrospectively, control and hf cats were calculated to be at 95% and 97% steady state, respectively. At the time blood samples were collected, hf cats were clinically compensated. Serum digoxin concentration ([dxn]) was determined by radioimmunoassay on samples drawn immediately before and 1, 2, 4, 8, 12, 24, 34, and 48 hours after digoxin administration. Measured and calculated values (peak, 8-hour, and mean [dxn]; elimination half-life [t½]; oral clearance; and hours during which [dxn] was in the toxic range) were not significantly different between control and hf cats.

To predict individual propensity for digoxin intoxication serum creatinine and urea concentrations and sulfobromophthalein dye retention were measured in control and hf cats prior to the onset of treatment with digoxin. There was no statistically significant correlation between serum creatinine and urea concentrations when compared with sulfobromophthalein dye retention nor between any of these values and digoxin peak, 8-hour, and mean concentrations or t½, oral clearance, or hours during which [dxn] was in the toxic range. Mean serum creatinine and urea nitrogen concentrations were significantly greater (P < 0.01) and sulfobromophthalein dye retention approached significant prolongation (P < 0.06) in hf cats, compared with that in control cats. All hf cats with sulfobromophthalein dye retention > 5% at 30 minutes became digoxtn-intox-icated, on the basis of [dxn]; no hf cats with normal sulfobromophthalein dye retention became intoxicated.

In compensated heart failure, digoxin pharmacokinetic properties are not altered beyond that expected when concurrent antithrombotic and offloading treatments with aspirin, furosemide, and commercial low-saltdiet are used. In addition, digoxin treatment q 48 h produces adequate serum concentrations in the cat, with steady state being reached after approximately 10 days of digoxin treatment in hf cats given concomitant treatment. Digoxin toxicosis can be expected in approximately 50% of animals given digoxin tablets at a dosage of 0.01 mg/kg, q 48 h, with the additional treatment described. Because of individual variation, [dxn] should be monitored to minimize digoxin toxicity and maximize its therapeutic efficacy. Blood samplings 8 hours after digoxin administration, after attaining approximate steady-state conditions in the animal, is recommended. Although serum urea and creatinine concentrations and sulfobromophthalein dye retention did not predict digoxin pharmacokinetic properties, the latter test may be useful in determining which cats will become digoxin-intoxicated.