In vivo effects of tepoxalin, an inhibitor of cyclooxygenase and lipoxygenase, on prostanoid and leukotriene production in dogs with chronic osteoarthritis.
OBJECTIVE
To evaluate in vivo effects of tepoxalin, an inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX), on prostaglandin (PG) and leukotriene production in osteoarthritic dogs.


METHODS
7 mixed-breed adult dogs with chronic unilateral arthritis of a stifle joint.


METHODS
Dogs were treated in accordance with a randomized 3-way crossover design. Each dog received an inert substance, meloxicam, or tepoxalin for 10 days. On day 0 (baseline), 3, and 10, dogs were anesthetized and samples of blood, stifle joint synovial fluid, and gastric mucosa were collected. Concentrations of PGE2 were measured in synovial fluid and after lipopolysaccharide stimulation of whole blood; PGE1 and PGE2 synthesis was measured in gastric mucosa. Thromboxane B2 (TxB2) concentration was measured in whole blood. Leukotriene B4 (LTB4) concentration was determined in gastric mucosa and in whole blood after ex vivo stimulation with a calcium ionophore.


RESULTS
Tepoxalin significantly decreased LTB4 concentrations in the blood and gastric mucosa at day 10 and TxB2 concentrations in the blood and PGE2 in the gastric mucosa and synovial fluid at days 3 and 10, compared with baseline values. Meloxicam significantly decreased PGE2 concentrations in the blood at days 3 and 10 and synovial fluid at day 3. Meloxicam also decreased PGE1 and PGE2 synthesis in the gastric mucosa at day 3. Meloxicam did not affect LTB4 synthesis in the blood or LTB4 concentrations in the gastric mucosa.


CONCLUSIONS
Tepoxalin has in vivo inhibitory activity against COX-1, COX-2, and 5-LOX in dogs at the current approved recommended dosage.
Agnello
Kimberly A
KA
Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Reynolds
Lisa R
LR
Budsberg
Steven C
SC
D000704:Analysis of Variance; D000818:Animals; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy* / Q000378:metabolism; D004285:Dogs; D015289:Leukotrienes / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077239:Meloxicam; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D011453:Prostaglandins / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013843:Thiazines; D013844:Thiazoles
D016861:Cyclooxygenase Inhibitors; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D011720:Pyrazoles; D013843:Thiazines; D013844:Thiazoles; C073135:tepoxalin; D000077239:Meloxicam