Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers

Steady-state inhibitory activity of rofecoxib (Vioxx(TM)) on COX-2 versus C OX-I was compared with that of commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) in 76 healthy volunteers randomized to placebo, rofecoxib 1 2.5 mg qd, rofecoxib 25 mg qd, diclofenac 50 mg tid, ibuprofen 800 mg tid, sodium naproxen 550 mg bid, or meloxicam 15 mg qd. All of these doses inclu de the high end of the approved clinical dose range. Ex vivo whole-blood as says were used to determine the effect on COX-2 and COX-1 activity, respect ively. Urinary prostanoids were also measured. Mean inhibition of COX-2 (me asured as the weighted average inhibition [WAI] of lipopolysaccharide [LPS] -induced PGE(2) generation over 8 hours on day 6 vs. baseline) was -2.4%, 6 6.7%, 69.2%, 77.5%, 93.9%, 71.4%, and 71.5% for placebo, rofecoxib 12.5 mg, rofecoxib 25 mg, meloxicam, diclofenac, ibuprofen, and naproxen, respectiv ely. Corresponding values for mean inhibition of COX-I (measured as TXB2 ge neration in clotting whole blood) were -5.15%, 7.98%, 6.65%, 53.3%, 49.5%, 88.7%, and 94.9%. Rofecoxib had no significant effect on urinary excretion of 11-dehydro TXB2, a COX-1-derived product. These data support the content ion that rofecoxib is the only drug of the regimens tested that uniquely in hibits COX-2 without affecting COX-I. (C) 2000 the American College of Clin ical Pharmacology.