[Effect of itraconazole on digoxin clearance in patients with congestive heart failure]

We showed a digoxin-itraconazole interaction in three patients in whom digoxin serum concentrations were increased. Their electrocardiograms revealed arrhythmias such as ventricular premature contraction, atrioventricular block, and ST depression. The elimination half-life of digoxin in case 3 patient who continued itraconazole therapy was 8.4 days, which was estimated by nonlinear least squares method from the serum concentrations of digoxin versus time curve. In order to evaluate the influence of itraconazole on pharmacokinetic parameters of digoxin, we estimated digoxin clearance by the Bayesian method using the population pharmacokinetic parameters in Japanese patients. During the concomitant use of itraconazole and digoxin, the digoxin clearance in all patients decreased to 50.5 +/- 8.8% (mean +/- S.D.) of the clearance without itraconazole. When digoxin and itraconazole are used concomitantly, careful monitoring of digoxin serum concentrations is necessary. Based on our results of digoxin clearance evaluation, the dose of digoxin should be reduced to 50% of original dose after itraconazole is started, and digoxin serum concentration might be controlled at the same level before the concomitant use.