Digoxin Toxicity : Evaluation in Clinical Practice with Pharmacokinetic Correlations.

OBJECTIVE: To evaluate digoxin pharmacokinetic parameters using Bayesian estimation in 60 patients, and to identify factors that appeared to affect the risk of digoxin toxicity.

PATIENTS AND METHODS: 60 patients with serum digoxin concentrations were evaluated retrospectively. We collected demographic, clinical and laboratory data, and information on concurrent medications and clinical and electrocardiographic features of digoxin toxicity. The incidence of digoxin toxicity was evaluated in 50 patients. Serum digoxin concentrations were measured with fluorescence polarisation immunoassay Individual pharmacokinetic parameters were estimated by Bayesian method using Abbottbase Pharmacokinetic Systems.

RESULTS: Signs of digoxin toxicity were present in 23 patients (46%). Patients without signs of digoxin toxicity had a significantly lower mean serum digoxin concentration than patients with signs, 1.99 ± 0.9 μg/L vs 2.7 ± 1.5 μ.g/L, respectively (p = 0.047). Patients with serum digoxin concentrations >2.2 μg/L differed significantly from those with values ≤2.2 μg/L, respectively, for the following parameters: age (82.0 ± 8.0 vs 72.0 ± 16.0 years; p = 0.005), serum creatinine levels (133.0 ± 55.0 vs 106.0 ± 26.0 μmo1/L; p = 0.012), bodyweight (57.4 ± 12.8 vs 69.2 ± 17.8kg; p = 0.01), volume of distribution (208.5 ± 89.5 vs 315.7 ± 91.2L; p = 0.0001), total clearance (1.60 ± 0.65 vs 3.4 ± 1.5 L/h; p = 0.0001), and elimination half-life (94.2 ± 28.6 vs 72.4 ± 16.7h; p = 0.001). Estimation of optimal dose showed that the doses recommended in intoxicated patients should be 3.5 times lower to reach the therapeutic range.

CONCLUSION: Digoxin concentrations were higher in patients with toxicity. Older age enhanced the risk of digoxin toxicity. Monitoring digoxin concentrations may help to confirm suspected digitalis toxicity.