Objective: To evaluate the extent of human cyclooxygenase-l (COX-1) inhibit
ion by meloxicam, which has been reported to preferentially inhibit cycloox
ygenase-2 (COX-2), The effects of meloxicam were compared with those of dic
lofenac, a nonselective COX inhibitor.
Methods: COX-1 inhibition was determined by measuring thromboxane B-2 (TXB2
)-generation from clotting whole blood ex vivo after single oral doses of 7
.5 and 15 mg meloxicam and 75 mg diclofenac and at steady state (15 mg melo
xicam daily and 150 mg diclofenac daily). The effect was expressed as perce
ntage inhibition of serum TXB2 generation and was directly related to the s
erum drug concentration with use of a standard sigmoidal E-max model.
Results: In terms of inhibition of TXB2 generation, diclofenac was about 1
order of magnitude more potent than meloxicam, indicated by a diclofenac EC
50 (concentration of drug required to cause 50% of maximum effect) that was
about 10 times lower than that of meloxicam (EC50 diclofenac single doses:
37.50 +/- 29.64; EC50 meloxicam single doses: 677.50 +/- 189.08), However,
serum concentrations of meloxicam after administration of 15 mg were appro
ximately 10-fold higher than those of diclofenac, Therefore there was no st
atistically significant difference in the area under the effect time curve
(P = .115) and the mean effect (P = .424) between meloxicam and diclofenac,
The EC50 of both drugs was significantly higher at steady state (diclofena
c steady state: 87.07 +/- 55.24 ng/mL; meloxicam steady state: 1850.12 +/-
829.93 ng/mL) than after a single dose (P < .001).
Conclusion: These data show that meloxicam inhibits TXB2 generation at clin
ically relevant doses, although less potently than diclofenac. Thus our dat
a suggest that the COX-2 preference of meloxicam observed in vitro may not
result in clinical advantages when the higher dose of 15 mg is needed. Beca
use of the increase in EC50 at steady state, COX-1 is relatively spared whe
n the lower dose of 7.5 mg is administered.