Assessment of pharmacokinetic and pharmacodynamic drug interactions between nefazodone and digoxin in healthy male volunteers.

The effect of nefazodone on pharmacokinetic and pharmacodynamic parameters of digoxin were evaluated in an open, randomized, multiple-dose, three-way crossover study of 18 healthy male volunteers. The volunteers received nefazodone alone (200 mg twice daily), digoxin alone (0.2 mg daily), or nefazodone combined with digoxin during three 8-day treatment periods, with a single dose on the ninth day. There was a 10-day washout period between treatment periods. Coadministration of nefazodone with digoxin had no effect on the frequency and severity of adverse events compared with those observed with either drug alone. Steady-state area under the concentration-time curve (AUC) and peak (Cmax) and trough (Cmin) concentrations of digoxin were significantly higher (15%, 29%, and 27%, respectively) after coadministration of nefazodone/digoxin than after administration of digoxin. Despite these increases, no clinically significant changes in vital signs, heart rate, or PR, QRS, and QT intervals on the electrocardiogram occurred after coadministration from those measured after digoxin monotherapy. Coadministration did not affect the pharmacokinetics of nefazodone or its metabolites (hydroxynefazodone, m-chlorophenylpiperazine, triazole dione). Because digoxin has a narrow therapeutic index, monitoring of plasma digoxin levels and appropriate adjustment of dosage are recommended when nefazodone and digoxin are administered concurrently.

RCT Entities:   Population Interventions Outcomes