The effect of chronic administration of citalopram on the single oral dose pharmacokinetics of digoxin was evaluated in 11 healthy adult subjects in an open, one-way crossover study. Subjects received 1 mg digoxin on day 1. Serial blood samples and total urine were collected over 192 hours, followed by an 11-day washout period. On days 22 through 50, subjects received 40 mg citalopram once daily. On day 43, a single dose of 1 mg digoxin was coadministered; again, serial blood samples and total urine were collected over 192 hours after the digoxin dose. There were no statistically significant differences in any of the digoxin pharmacokinetic parameters (AUC(0-->24), AUC(0-->infinity), Cmax, tmax, t(1/2), CL/F, CLrenal, and Ae(0-->infinity)), and the 90% confidence intervals for treatment differences for the parameters (except for tmax) were all within 80% to 125%. Concomitant digoxin administration did not significantly affect citalopram pharmacokinetics. The treatment was well tolerated by all subjects; no serious adverse events and no clinically significant ECG changes were observed. These data suggest that it is unlikely that concomitantly administered citalopram would have any significant effect on serum digoxin concentrations in patients who are receiving chronic digoxin therapy.