Digoxin toxicity - Evaluation in clinical practice with pharmacokinetic correlations

Objective: To evaluate digoxin pharmacokinetic parameters using Bayesian es timation in 60 patients, and to identify factors that appeared to affect th e risk of digoxin toxicity. Patients and Methods: 60 patients with serum digoxin concentrations were ev aluated retrospectively. We collected demographic, clinical and laboratory data, and information on concurrent medications and clinical and electrocar diographic features of digoxin toxicity. The incidence of digoxin toxicity was evaluated in 50 patients. Serum digoxin concentrations were measured wi th fluorescence polarisation immunoassay. Individual pharmacokinetic parame ters were estimated by Bayesian method using Abbottbase Pharmacokinetic Sys tems. Results: Signs of digoxin toxicity were present in 23 patients (46%). Patie nts without signs of digoxin toxicity had a significantly lower mean serum digoxin concentration than patients with signs, 1.99 +/- 0.9 mug/L vs 2.7 /- 1.5 mug/L, respectively (p = 0.047). Patients with serum digoxin concent rations >2.2 mug/L differed significantly from those with values 12.2 mug/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 mu mol/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 +/- 91.21,; 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). Est imation of optimal dose showed that the doses recommended in intoxicated pa tients should be 3.5 times lower to reach the therapeutic range. Conclusion: Digoxin concentrations were higher in patients with toxicity. O lder age enhanced the risk of digoxin toxicity. Monitoring digoxin concentr ations may help to confirm suspected digitalis toxicity.