Comparative inhibitory activity of etoricoxib, celecoxib, and diclofenac on COX-2 versus COX-1 in healthy subjects.

We determined cyclo-oxygenase-1 and cyclo-oxygenase-2 inhibition in healthy middle-aged subjects (41-65 years) randomly assigned to four 7-day treatment sequences of etoricoxib 90 mg every day, celecoxib 200 mg twice a day, diclofenac 75 mg twice a day, or placebo in a double-blind, randomized, 4-period crossover study. Maximum inhibition of thromboxane B(2) (cyclo-oxygenase-1 activity) in clotting whole blood on day 7 (0-24 hours postdose) was the primary endpoint. Inhibition of lipopolysaccharide-induced prostaglandin E(2) in whole blood (cyclo-oxygenase-2 activity) was assessed on day 7 (0-24 hours postdose) as a secondary endpoint. Diclofenac had significantly greater maximum inhibition of thromboxane B(2) versus each comparator (P < .001); placebo 2.4% (95% confidence interval: -8.7% to 12.3%), diclofenac 92.2% (91.4% to 92.9%), etoricoxib 15.5% (6.6% to 23.5%), and celecoxib 20.2% (11.5% to 28.1%). Prostaglandin E(2) synthesis was inhibited with a rank order of potency of diclofenac > etoricoxib > celecoxib. In summary, at doses commonly used in rheumatoid arthritis, diclofenac significantly inhibits both cyclo-oxygenase-1 and cyclo-oxygenase-2, whereas etoricoxib and celecoxib significantly inhibit cyclo-oxygenase-2 and do not substantially inhibit cyclo-oxygenase-1.

Effects of etoricoxib and comparator nonsteroidal anti-inflammatory drugs on urinary sodium excretion, blood pressure, and other renal function indicators in elderly subjects consuming a controlled sodium diet.

This multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessed renal function during dosing with etoricoxib 90 mg daily, celecoxib 200 mg twice daily, and naproxen 500 mg twice daily. Male and female subjects 60 to 81 years old (n = 85), in sodium balance on a controlled, normal sodium diet, were treated for 15 days. There were no clinically meaningful between-treatment differences in urinary sodium excretion, creatinine clearance, body weight, or serum electrolytes during the 2 weeks of treatment. Etoricoxib and celecoxib had no effect on the urinary thromboxane metabolite, 11-dehydrothromboxane B(2), while significantly decreasing the urinary prostacyclin metabolite, 2,3-dinor-6-keto PGF(1alpha). Decreases were greater for both metabolites following naproxen. Ambulatory systolic blood pressures were significantly higher than placebo for all treatments, with moderately greater increases for etoricoxib relative to other active treatments on day 14. Ambulatory diastolic blood pressures were significantly higher than placebo for etoricoxib and naproxen but not for celecoxib.