Objective—To evaluate cyclooxygenase (COX) selectivity
of several nonsteroidal anti-inflammatory drugs
(NSAID) in canine blood in vitro.
Animals—11 healthy adult male hound crosses.
Procedure—9 NSAID were studied at 5 concentrations.
Thromboxane B2 (TxB2) was assayed as a
measure of COX-1 activity in clotted blood.
Prostaglandin E2 (PGE2) was assayed as a measure
of COX-2 activity in heparinized, lipopolysaccharide
(LPS)-stimulated blood. All assays were competitive
ELISA tests. Cyclooxygenase selectivity was
expressed as a ratio of the concentration of an
NSAID that inhibited 50% of the activity (IC50) of
COX-1 to the IC50 of COX-2. A separate ratio of the
concentration that inhibited 80% of COX activity
(IC80) was also determined. A ratio of
< 1.0 indicated selectivity for COX-1, whereas a
ratio of > 1.0 indicated COX-2 selectivity.
Results—Ketoprofen, aspirin, and etodolac were
COX-1 selective. Piroxicam, meloxicam, and carprofen
had COX-2 selectivity. The IC50 and IC80 values
were similar for most NSAID.
Conclusion and Clinical Relevance—This methodology provides repeatable
data from individual dogs and is comparable to results
of previous in vitro and ex vivo models. Findings are
also consistent with those of canine studies performed
in vivo, suggesting that this is a viable in vitro
assessment of the COX selectivity of NSAID in dogs.
(Am J Vet Res 2002;63:91–94)
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)