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Comparative Inhibitory Activity of Etoricoxib, Celecoxib, and Diclofenac on COX‐2 Versus COX‐1 in Healthy Subjects
Author(s) -
Schwartz Jules I.,
Dallob Aimee L.,
Larson Patrick J.,
Laterza Omar F.,
Miller Jutta,
Royalty Jane,
Snyder Karen M.,
Chappell Derek L.,
Hilliard Deborah A.,
Flynn Mary E.,
Cavanaugh Paul F.,
Wagner John A.
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008317590
Subject(s) - etoricoxib , celecoxib , diclofenac , pharmacology , rofecoxib , medicine , crossover study , placebo , thromboxane , cyclooxygenase , chemistry , anesthesia , biochemistry , enzyme , platelet , alternative medicine , pathology
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.