Objective—To determine potency and selectivity of
nonsteroidal anti-inflammatory drugs (NSAID) and
cyclooxygenase- (COX-) specific inhibitors in whole
blood from horses, dogs, and cats.
Sample Population—Blood samples from 30 healthy
horses, 48 healthy dogs, and 9 healthy cats.
Procedure—Activities of COX-1 and COX-2 were
determined by measuring coagulation-induced thromboxane
B2 and lipopolysaccharide-induced
prostaglandin E2 concentrations, respectively, in
whole blood with and without the addition of various
concentrations of phenylbutazone, flunixin meglumine,
ketoprofen, diclofenac, indomethacin, meloxicam,
methylsulfonylphenyl]-thiophene (DuP 697), 5,5-
phenyl-2(5H)-furan one (DFU), 3-(3,4-difluorophenyl)-
and celecoxib. Potency of each test compound
was determined by calculating the concentration that
resulted in inhibition of 50% of COX activity (IC50).
Selectivity was determined by calculating the ratio of
IC50 for COX-1 to IC50 for COX-2 (COX-1/COX-2 ratio).
Results—The novel compound DFU was the most
selective COX-2 inhibitor in equine, canine, and feline
blood; COX-1/COX-2 ratios were 77.5, 74, and 69,
respectively. Carprofen was the weakest inhibitor of
COX-2, compared with the other COX-2 selective
inhibitors, and did not inhibit COX-2 activity in equine
blood. In contrast, NSAID such as phenylbutazone
and flunixin meglumine were more potent inhibitors
of COX-1 than COX-2 in canine and equine blood.
Conclusions and Clinical Relevance—The novel
COX-2 inhibitor DFU was more potent and selective in
canine, equine, and feline blood, compared with
phenylbutazone, flunixin meglumine, and carprofen.
Compounds that specifically inhibit COX-2 may result
in a lower incidence of adverse effects, compared
with NSAID, when administered at therapeutic
dosages to horses, dogs, and cats. (Am J Vet Res