JP Punke, LR Reynolds, AL Speas, SC Budsberg.
University of Georgia, Athens, GA, United States

ACVS Abstract 2007 

The study objective was to examine early in vivo effects of firocoxib, tepoxalin and meloxicam on prostaglandin synthesis in osteoarthritic dogs. A randomized 4 way crossover study design was used. Dogs received placebo, meloxicam, tepoxalin and firocoxib for 7 days, followed by a washout period. On days 0, 2, 4, and 7, whole blood and gastric and duodenal biopsies were collected. Prostaglandin E2 (PGE2) concentrations were measured in whole blood, and in the gastric and duodenal mucosa.

Thromboxane B2 (TxB2) was measured in serum. Concentrations of PGE2 and TxB2, were all determined via ELISA. A repeated measures ANOVA was used to compare data within and between groups. All drugs decreased plasma PGE2 compared to placebo at all time periods. Firocoxib decreased plasma PGE2 compared to baseline at 2, 4, and 7 days, and decreased plasma PGE2 significantly more than tepoxalin at all time periods. Meloxicam decreased PGE2 compared to baseline at 4 and 7 days.

Firocoxib and meloxicam did not alter TXB2 levels compared to baseline or placebo over the study period. Tepoxalin decreased TXB2 at all time periods compared to baseline, placebo, firocoxib and meloxicam. Firocoxib and meloxicam did not alter PGE2 synthesis in gastric or duodenal mucosa compared to baseline and placebo at any time during the study.

Tepoxalin decreased PGE2 synthesis in gastric mucosa compared to baseline, placebo, meloxicam and firocoxib at all time periods. Firocoxib and meloxicam exhibit cyclooxygenase-1 sparing effects in vivo. Duodenal mucosa PGE2 synthesis is much lower than that in gastric mucosa.