Evaluation of the pharmacokinetics of digoxin in healthy subjects receiving etoricoxib.
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.
Schwartz
Jules I
JI
Merck Research Laboratories, Rahway, NJ 07065-0900, USA. jules_schwartz@merck.com
Agrawal
Nancy G B
NG
Wehling
Martin
M
Musser
Bret J
BJ
Gumbs
Carol P
CP
Michiels
Nicole
N
De Smet
Marina
M
Wagner
John A
JA
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
D002301:Cardiac Glycosides; D016861:Cyclooxygenase Inhibitors; D011725:Pyridines; D013450:Sulfones; D004077:Digoxin; D000077613:Etoricoxib