E11 - Effects of Phenylbutazone, Firocoxib, and Dipyrone on Furosemide-Induced Diuresis in Horses

Abstract: Background: Administration of NSAIDs to horses to control inflammation via cyclooxygenase enzymes (COX) inhibition may have adverse renal effects. Both COX-1 and COX-2 regulate renal blood flow, glomerular filtration, and urinary concentrating ability. Treatment with phenylbutazone (a COX-1 inhibitor) has been demonstrated to decrease the diuretic and natriuretic effects of furosemide by nearly 30%. The effect of COX-2 specific inhibitors (firocoxib) and atypical NSAIDs (dipyrone) on the renal effects of furosemide in horses are unknown.

Hypothesis: Furosemide-induced diuresis after pre-treatment with firocoxib or dipyrone is diminished to a lesser extent than after treatment with phenylbutazone.

Animals: Eight healthy mares.

Methods: Each mare received four treatments in a replicated 4 x 4 Latin Square design: furosemide alone (F), furosemide and firocoxib (FF), furosemide and dipyrone (FD), and furosemide and phenylbutazone (FP). After 2 days of NSAID treatment at recommended dosages, ureteral catheters were placed for continual urine collection. After a 30-minute baseline collection period, furosemide (1.0 mg/kg, IV) was administered, and urine and blood samples were collected for 4 hours. Data were assessed by one-way repeated measures ANOVA.

Results: 4-hour urine volume was decreased (P < 0.001) 20-25% after pretreatment with all NSAIDs, as compared to F, but there were no differences between FF, FD, or FP. Variability in individual responses to furosemide administration after pretreatment with different NSAIDs was observed.

Conclusions and clinical importance: Though COX-2 selective NSAIDs have less adverse GI effects in horses, our data suggest there are minimal differences in effects on furosemide-induced diuresis.