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

Abstract

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 &#xd7;&#x2009;4 Latin Square design: furosemide alone (FU), furosemide and phenylbutazone (PB), furosemide and firocoxib (FX), and furosemide and dipyrone (DP). After 24&#x2009;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&#x2009;mg/kg, IV) was administered, and urine and blood samples were collected for 4&#x2009;hours. Data were assessed by repeated measures ANOVA. RESULTS: Four-hour urine volume was (mean&#x2009;&#xb1;&#x2009;SD) ~25% less (P&#x2009;<&#x2009;.001) after pretreatment with all NSAIDs (PB 19.1&#x2009;&#xb1;&#x2009;2.1&#x2009;mL/kg, FX 17.7&#x2009;&#xb1;&#x2009;3.5&#x2009;mL/kg, DP 19.1&#x2009;&#xb1;&#x2009;3.9&#x2009;mL/kg), as compared to FU (23.4&#x2009;&#xb1;&#x2009;5.1&#x2009;mL/kg) (P&#x2009;<&#x2009;.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.