In vivo effects of carprofen, deracoxib, and etodolac on prostanoid production in blood, gastric mucosa, and synovial fluid in dogs with chronic osteoarthritis.
OBJECTIVE
To evaluate in vivo activity of carprofen, deracoxib, and etodolac on prostanoid production in several target tissues in dogs with chronic osteoarthritis.


METHODS
8 dogs with chronic unilateral osteoarthritis of the stifle joint.


METHODS
Each dog received carprofen, deracoxib, or etodolac for 10 days with a 30- to 60-day washout period between treatments. On days 0, 3, and 10, prostaglandin (PG) E2 concentrations were measured in lipopolysaccharide-stimulated blood, synovial fluid, and gastric mucosal biopsy specimens; PGE1 concentrations were measured in gastric mucosal biopsy specimens; and thromboxane B2 (TXB2) was evaluated in blood.


RESULTS
Carprofen and deracoxib significantly suppressed PGE2 concentrations in blood at days 3 and 10, compared with baseline, whereas etodolac did not. None of the drugs significantly suppressed TXB2 concentrations in blood or gastric PGE1 synthesis at any time point. All 3 drugs significantly decreased gastric synthesis of PGE2 at day 3 but not day 10 of each treatment period. All 3 drugs decreased synovial fluid PGE2 concentrations in the affected and unaffected stifle joints at days 3 and 10.


CONCLUSIONS
Results indicate that carprofen and deracoxib act in vivo on target tissues as COX-1-sparing drugs by sparing gastric PGE1 and PGE2 synthesis and production of TXB2 by platelets. Etodolac also appears to be COX-1 sparing but may have variable effects on COX-2 depending on the tissue. In gastric mucosa and synovial fluid, there were no significant differences in PG production between compounds at recommended concentrations.
Sessions
John K
JK
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Reynolds
Lisa R
LR
Budsberg
Steven C
SC
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone / Q000096:biosynthesis* / Q000097:blood; D004283:Dog Diseases / Q000188:drug therapy* / Q000378:metabolism; D004285:Dogs; D004334:Drug Administration Schedule; D017308:Etodolac / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism*; D010003:Osteoarthritis / Q000188:drug therapy / Q000662:veterinary*; D013449:Sulfonamides / Q000494:pharmacology; D013582:Synovial Fluid / Q000378:metabolism*; D000096926:Benzenesulfonamides
D002227:Carbazoles; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D017308:Etodolac; D013449:Sulfonamides; C007005:carprofen; C471996:deracoxib; D000096926:Benzenesulfonamides