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Effects of compensated heart failure on digoxin pharmacokinetics in cats
C E Atkins1, P S Snyder, B W Keene
1Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706.
Insights
Compensated heart failure (HF) in cats does not significantly alter digoxin pharmacokinetics, indicating similar drug efficacy and safety profiles between healthy and compensated HF cats. This suggests careful dosing is key for both groups.
Area of Science:
- Veterinary Pharmacology
- Cardiology
- Pharmacokinetics
Background:
- Heart failure (HF) can alter drug pharmacokinetics.
- Digoxin is a cardiac glycoside used in treating heart conditions.
- Understanding digoxin's behavior in compensated HF is crucial for feline treatment.
Purpose of the Study:
- To evaluate the pharmacokinetic properties of digoxin in cats with compensated heart failure.
- To compare digoxin's peak, half-life, and clearance in healthy versus HF cats.
- To assess predictors of digoxin toxicity in cats.
Main Methods:
- Six cats with dilated cardiomyopathy (compensated HF) and six control cats received digoxin (0.01 mg/kg q 48 h).
- Concomitant medications included aspirin, furosemide, and a low-salt diet.
- Serum digoxin concentrations were measured over 48 hours post-administration; creatinine, urea, and sulfobromophthalein retention were also assessed.
Main Results:
- No significant differences were found in digoxin peak concentration, 8-hour concentration, mean concentration, elimination half-life, or oral clearance between control and HF cats.
- HF cats showed significantly higher mean serum creatinine and urea nitrogen concentrations.
- Sulfobromophthalein dye retention was prolonged in HF cats, approaching statistical significance.
Conclusions:
- Compensated heart failure in cats does not significantly affect digoxin pharmacokinetics.
- Digoxin dosing and monitoring strategies may be similar for healthy and compensated HF cats.
- Renal function markers (creatinine, urea) and liver function (sulfobromophthalein) were altered in HF cats, but did not correlate with digoxin pharmacokinetics.
Abstract:
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 [t1/2]; 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 t1/2, oral clearance, or hours during which [DXN] was in the toxic range. Mean serum creatinine and urea nitrogen concentrations were significantly greater (P less than 0.01) and sulfobromophthalein dye retention approached significant prolongation (P less than 0.06) in HF cats, compared with that in control cats.(ABSTRACT TRUNCATED AT 250 WORDS)