Effect of rofecoxib on the pharmacokinetics of digoxin in healthy volunteers

The authors examined the effect of the cyclooxygenase-2 (COX-2) inhibitor, rofecoxib, at steady state on the pharmacokinetics of digoxin following a s ingle dose in healthy subjects. Each healthy subject (N = 10) received rofe coxib (75 mg once daily) or placebo for 11 days in a double-blind, randomiz ed, balanced, two-period crossover study. A single 0.5 mg oral dose of digo xin elixir was administered on the 7th day of each 11-day period. Each trea tment period was separated by 14 to 21 days. Samples for plasma and urine i mmunoreactive digoxin concentrations were collected through 120 hours follo wing the digoxin dose. No statistically significant differences between tre atment groups were observed for any of the calculated digoxin pharmacokinet ic parameters. For digoxin AUC((0-infinity)), AUC((0-24)), and C-max, the g eo metric mean ratios (90% confidence interval) for (rofecoxib + digoxin/pl acebo + digoxin) were 1.04 (0.94, 1.14), 1.02 (0.94, 1.09), and 1.00 (0.91, 1.10), respectively. The digoxin median t(max) was 0.5 hours for both trea tments. The harmonic mean elimination half-life was 45.7 and 43.4 hours for rofecoxib + digoxin and placebo + digoxin treatments, respectively. Digoxi n is eliminated renally. The mean (SD) cumulative urinary excretion of immu noreactive digoxin after concurrent treatment with rofecoxib or placebo was 228.2 (+/- 30.8) and 235.1 (+/- 39.1) mug/120 hours, respectively. Transie nt and minor adverse events occurred with similar frequency on placebo and rofecoxib treatments, and no treatment-related pattern was apparent. Rofeco xib did not influence the plasma pharmacokinetics or renal elimination of a single oral dose of digoxin. Journal of Clinical Pharmacology 2001;41:107- 122 (C) 2001 the American College of Clinical Pharmacology.