title: Evaluation of the pharmacokinetics of digoxin in healthy subjects receiving etoricoxib.
abstract: OBJECTIVE
  Digoxin is a commonly prescribed cardiac glycoside with a narrow therapeutic index. The aim was to investigate whether the cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug etoricoxib affects the steady-state pharmacokinetics of digoxin.
  
  
  METHODS
  This was a double-blind, randomized, placebo-controlled, two-period cross-over study. In each period, 14 healthy volunteers ranging in age from 21 to 35 years received oral digoxin 0.25 mg daily and were randomized to either etoricoxib 120 mg or matching placebo tablets once daily for 10 days. Trough digoxin plasma concentrations were analysed by linear regression to examine digoxin accumulation over time.
  
  
  RESULTS
  The geometric mean ratios (etoricoxib/placebo) for AUC(0-24h), C(max) and urinary excretion were 1.06 (90% confidence interval 0.97, 1.17), 1.33 (1.21, 1.46) and 1.10 (1.00, 1.20), respectively. The median (range) for digoxin T(max) (h) values with etoricoxib and placebo were 0.5 (0.5, 1.5) and 1.0 (0.5, 1.5), respectively. Steady-state digoxin plasma concentrations were achieved by day 7 in each treatment period. No serious adverse experiences were reported.
  
  
  CONCLUSIONS
  Although etoricoxib 120 mg did produce an approximately 33% increase in digoxin C(max), this increase does not appear to be clinically meaningful, as cardiotoxicity with digoxin has been associated with elevations in steady-state rather than peak concentrations. From these results, it appears that etoricoxib does not cause any changes in digoxin steady-state pharmacokinetics that would necessitate a dose adjustment.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065-0900, USA. jules_schwartz@merck.com
authors.forename: Jules I
authors.initials: JI
authors.lastname: Schwartz
authors.forename: Nancy G B
authors.initials: NG
authors.lastname: Agrawal
authors.forename: Martin
authors.initials: M
authors.lastname: Wehling
authors.forename: Bret J
authors.initials: BJ
authors.lastname: Musser
authors.forename: Carol P
authors.initials: CP
authors.lastname: Gumbs
authors.forename: Nicole
authors.initials: N
authors.lastname: Michiels
authors.forename: Marina
authors.initials: M
authors.lastname: De Smet
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002301:Cardiac Glycosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004812:Epidemiologic Methods; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013450:Sulfones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D002301:Cardiac Glycosides; D016861:Cyclooxygenase Inhibitors; D011725:Pyridines; D013450:Sulfones; D004077:Digoxin; D000077613:Etoricoxib