The effect of multiple oral doses of montelukast, a cysLT1 receptor antagonist, on the pharmacokinetics of oral digoxin was studied in healthy male volunteers in a randomized double-blind two-period crossover study. Subjects received 10 mg of montelukast or placebo daily for 11 days. On day 7, they received a single 0.5 mg oral dose of digoxin elixir. The pharmacokinetic parameters of digoxin (AUC0-->24' AUC0-->infinity' Cmax' tmax' t1/2) and cumulative urinary excretion over 120 hours were not affected by the multiple doses of montelukast. The 90% confidence interval for each of these parameters fell within prespecified clinically acceptable bounds. Side effects were mild and transient. This suggests that concurrent administration of montelukast and digoxin was well tolerated. Concurrent treatment with montelukast has no effect on the pharmacokinetics of digoxin.