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. Animals-7 mixed-breed adult dogs with chronic unilateral arthritis of a stifle joint. Procedure-Dogs were treated in accordance with 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 PGE(2) were measured in synovial fluid and after lipopolysaccharide stimulation of whole blood; PGE(1) and PGE(2) synthesis was measured in gastric mucosa. Thromboxane B-2 (TxB(2)) concentration was measured in whole blood. Leukotriene B-4 (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 PGE(1) and PGE(2) 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 and Clinical Relevance-Tepoxalin has in vivo inhibitory activity against COX-1, COX-2, and 5-LOX in dogs at the current approved recommended dosage.