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Vol. 290, Issue 1, 276-280, July 1999
Department of Medicine and Aging, Division of Pharmacology,
University of Chieti "G. D'Annunzio" School of Medicine, Chieti,
Italy
We evaluated whether therapeutic blood levels of meloxicam are
associated with selective inhibition of monocyte cyclooxygenase (COX)-2
in vitro and ex vivo. Concentration-response curves for the inhibition
of monocyte COX-2 and platelet COX-1 were obtained in vitro after the
incubation of meloxicam with whole blood samples. Moreover, 11 healthy
volunteers received placebo or 7.5 or 15 mg/day meloxicam, each
treatment for 7 consecutive days, according to a randomized,
double-blind, crossover design. Before dosing and 24 h after the
seventh dose of each regimen, heparinized whole blood samples were
incubated with lipopolysaccharide (10 µg/ml) for 24 h at 37°C,
and prostaglandin E2 was measured in plasma as an index of
monocyte COX-2 activity. The production of thromboxane B2
in whole blood allowed to clot at 37°C for 60 min was assessed as an
index of platelet COX-1 activity. The administration of placebo did not
significantly affect plasma prostaglandin E2 (21.3 ± 7.5 versus 19.1 ± 4 ng/ml, mean ± S.D.,
n = 11) or serum thromboxane B2
(426 ± 167 versus 425 ± 150 ng/ml) levels. In contrast, the administration of 7.5 and 15 mg of meloxicam caused dose-dependent reductions in monocyte COX-2 activity by 51% and 70%, respectively, and in platelet COX-1 activity by 25% and 35%, respectively. Although the IC50 value of meloxicam for inhibition of COX-1 was
10-fold higher than the IC50 value of COX-2 in vitro, this
biochemical selectivity was inadequate to clearly separate the effects
of meloxicam on the two isozymes after oral dosing as a function of the
daily dose and interindividual variation in steady-state plasma levels.
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