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

Author(s): Schwartz JI, Dallob AL, Larson PJ, Laterza OF, Miller J, Royalty J, Snyder KM, Chappell DL, Hilliard DA, Flynn ME, Cavanaugh PF Jr, Wagner JA

Affiliation(s): Merck Research Laboratories, 126 East Lincoln Avenue, RY34-A500 (A5035), Rahway, NJ 07065, USA. jules_schwartz@merck.com

Publication date & source: 2008-06, J Clin Pharmacol., 48(6):745-54. Epub 2008 Apr 23.

Publication type: Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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.

Page last updated: 2008-11-03

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