Effects of Firocoxib and Tepoxalin on Healing in a Canine Gastric Mucosal Injury Model
The purpose of this study was to compare the effects of therapeutically dosed firocoxib and tepoxalin on gastric mucosal healing in dogs. We hypothesized that firocoxib would alter healing of induced gastric wounds.
Gastric body and pylorus lesions were induced via endoscopic biopsy in 6 adult dogs. The dogs were then treated with tepoxalin, firocoxib, or placebo for 7 days in a three way crossover study design. Wound healing was evaluated on days 2, 4, and 7 of treatment using endoscopic mucosal scoring of lesion appearance and size. Eicosanoid concentrations in plasma and at the mucosal lesion margins were determined on days 2, 4, and 7. Repeated measures analyses were performed. All hypotheses tested were 2-sided with P < 0.05. Multiple comparisons were adjusted for using a Tukey's test.
Significant treatment differences were noted in the pyloric lesion area measurements with firocoxib having larger lesions than placebo or tepoxalin. Pyloric mucosal prostaglandin E2 (PGE2) synthesis was significantly lower in dogs administered tepoxalin than in dogs administered either firocoxib or placebo. Compared to placebo, pyloric mucosal LTB4 levels in the tepoxalin and firocoxib groups trended to increase on day 7.
Despite larger pyloric lesions in the firocoxib treatment group, mucosal PGE2 production did not differ significantly from placebo. Conversely, the tepoxalin treatment group had significantly lower mucosal PGE2 production yet pyloric lesions were not significantly larger than the placebo group. In this study, suppression of PGE2 in tepoxalin treated dogs did not alter pyloric mucosal lesion healing compared to placebo.