Objective—To evaluate in vivo activityin dogs of
meloxicam or aspirin, previously shown in vitro to be a
selective cyclooxygenase-2 (COX-2) inhibitor (COX-1
sparing drug), or a nonselective COX inhibitor, respectively.
Animals—12 male dogs with unilateral osteoarthritis
of the stifle joint.
Procedure—Each dog was treated in a crossover
design with aspirin or meloxicam for 21 days.
Prostaglandin E2 (PGE2) concentrations were measured
at days 0 (baseline), 7, and 21 of each treatment
period in lipopolysaccharide (LPS)-stimulated blood,
synovial fluid collected by arthrocentesis, and endoscopic
gastric mucosal biopsy specimens.
Thromboxane B2 (TXB2) was evaluated in blood on
days 0, 7, and 21 of each treatment period.
Results—Aspirin administration significantly suppressed
PGE2 concentrations in blood, gastric
mucosa, synovial fluid, and suppressed TXB2 concentration
in blood at days 7 and 21. Meloxicam
administration significantly suppressed PGE2 concentrations
in blood and synovial fluid at days 7 and
21, but had no effect on concentrations of TXB2 in
blood or PGE2 in gastric mucosa. Suppression of
LPS-stimulated PGE2 concentrations in blood and
synovial fluid by aspirin and meloxicam administration
is consistent with activity against the COX-2
isoenzyme. Suppression of concentrations of PGE2
in the gastric mucosa and TXB2 in blood by aspirin
administration is consistent with activity against
COX-1. Meloxicam, in contrast, had a minimal effect
on functions mediated by COX-1.
Conclusions and Clinical Relevance—Meloxicam
acts in vivo in dogs as a COX-1 sparing drug on target
tissues by sparing gastric PGE2 synthesis while
retaining antiprostaglandin effects within inflamed
joints. (Am J Vet Res 2002;63:1527–1531)