Substituted benzimidazole inhibitors of the gastric H+/K+ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs. On the other hand, changes in intragastric pH might alter the absorption of other drugs. The primary aim of the present study was to determine whether pantoprazole modifies the steady-state serum concentrations of orally administered digoxin. Secondary aims were the influence of digoxin on the pharmacokinetics of pantoprazole as well as safety and tolerability. Eighteen healthy volunteers received a single oral dose of pantoprazole (40 mg) and serum concentrations were determined. Three to 10 days later, subjects received in a single-blind, randomized, crossover fashion oral beta-acetyldigoxin (0.2 mg) twice daily and concomitant oral pantoprazole (40 mg) or placebo once daily for 5 days. Serum concentrations of pantoprazole and digoxin were determined on day 5. Primary characteristics for confirmative assessment of no interaction were AUC and Cmax of digoxin. Lack of interaction in the sense of equivalence was concluded for both digoxin (with and without pantoprazole) and pantoprazole (with and without digoxin) as the 90%-confidence intervals of the respective AUC- and Cmax-ratios were within the equivalence range of 0.8-1.25. Pantoprazole did not influence the characteristic ECG modifications (T-wave) caused by digoxin. Both drugs were well tolerated and no adverse events or clinically relevant alterations in vital signs or clinical laboratory parameters were observed during treatment. In conclusion, pantoprazole and digoxin may be administered concomitantly without the need for dose adjustment.