Effects of phenylbutazone, firocoxib, and dipyrone on the diuretic response to furosemide in horses

Background: Treatment with phenylbutazone (nonselective COX inhibitor) decreases the diuretic and natriuretic effects of furosemide by nearly 30% but the effects of COX-2 specific inhibitors (firocoxib) and atypical NSAIDs (dipyrone) are unknown.Hypothesis: Furosemide-induced diuresis after pretreatment with firocoxib or dipyrone is diminished to a lesser extent than after pretreatment with phenylbutazone.Animals: Eight healthy mares. Methods: Each mare received 4 treatments in a prospective experimental crossover study using a replicated 4 x 4 Latin Square design: furosemide alone (FU), furosemide and phenylbutazone (PB), furosemide and firocoxib (FX), and furosemide and dipyrone (DP). After 24 hours 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 repeated measures ANOVA. Results: Four-hour urine volume was (mean +/- SD) similar to 25% less (P < .001) after pretreatment with all NSAIDs (PB 19.1 +/- 2.1 mL/kg, FX 17.7 +/- 3.5 mL/kg, DP 19.1 +/- 3.9 mL/kg), as compared to FU (23.4 +/- 5.1 mL/kg) (P < .001), but there were no differences between PB, FX, or DP. Interindividual variability in furosemide diuresis after pretreatment with different NSAIDs was observed. Conclusions and Clinical Importance: Though COX-2 selective NSAIDs and dipyrone might have less severe or fever gastrointestinal adverse effects in horses, our data suggest minimal differences in effects on furosemide-induced diuresis, and possibly, risk of nephrotoxicosis.