Effects of meloxicam and phenylbutazone on renal responses to furosemide, dobutamine, and exercise in horses

Sharanne L. Raidal Schools of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.

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Kris J. Hughes Schools of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.

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Amanda-Lee Charman Schools of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.

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Sharon G. Nielsen Computing and Mathematics, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.

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Jacqueline K. Phillips Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia.

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Glenys K. Noble Schools of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.

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Abstract

Objective—To compare the effects of 2 NSAIDs (phenylbutazone and meloxicam) on renal function in horses.

Animals—9 Thoroughbred or Standardbred mares (mean ± SD age, 5.22 ± 1.09 years [range, 2 to 12 years]; mean body weight, 470 ± 25 kg [range, 442 to 510 kg]).

Procedures—A randomized blinded placebo-controlled crossover study was conducted to examine the effects of treatment with phenylbutazone, meloxicam, or a placebo (control solution) on renal responses to the administration of furosemide, dobutamine, and exercise (15 minutes at 60% of maximum heart rate). Renal function was assessed by use of bilateral ureteral catheterization for simultaneous determination of creatinine clearance, sodium excretion, and urine flow rate.

Results—Both phenylbutazone and meloxicam attenuated diuresis and natriuresis and reduced glomerular filtration rate, compared with results for the control solution, when horses were treated with furosemide. Mean arterial blood pressure, urine flow rate, and glomerular filtration rate were increased during or after (or both) dobutamine infusion. Both NSAIDs reduced urine flow rate and sodium excretion associated with dobutamine infusion and exercise but had no effect on glomerular filtration rate.

Conclusions and Clinical Relevance—Responses to meloxicam, a cyclooxygenase (COX)-2 preferential agent, appeared comparable to those detected after phenylbutazone treatment, which suggested that COX-2 was the mediator of prostanoid-induced changes to renal function in horses and indicated that COX-2–preferential agents would be likely to have adverse renal effects similar to those for nonselective COX inhibitors in volume-depleted horses.

Abstract

Objective—To compare the effects of 2 NSAIDs (phenylbutazone and meloxicam) on renal function in horses.

Animals—9 Thoroughbred or Standardbred mares (mean ± SD age, 5.22 ± 1.09 years [range, 2 to 12 years]; mean body weight, 470 ± 25 kg [range, 442 to 510 kg]).

Procedures—A randomized blinded placebo-controlled crossover study was conducted to examine the effects of treatment with phenylbutazone, meloxicam, or a placebo (control solution) on renal responses to the administration of furosemide, dobutamine, and exercise (15 minutes at 60% of maximum heart rate). Renal function was assessed by use of bilateral ureteral catheterization for simultaneous determination of creatinine clearance, sodium excretion, and urine flow rate.

Results—Both phenylbutazone and meloxicam attenuated diuresis and natriuresis and reduced glomerular filtration rate, compared with results for the control solution, when horses were treated with furosemide. Mean arterial blood pressure, urine flow rate, and glomerular filtration rate were increased during or after (or both) dobutamine infusion. Both NSAIDs reduced urine flow rate and sodium excretion associated with dobutamine infusion and exercise but had no effect on glomerular filtration rate.

Conclusions and Clinical Relevance—Responses to meloxicam, a cyclooxygenase (COX)-2 preferential agent, appeared comparable to those detected after phenylbutazone treatment, which suggested that COX-2 was the mediator of prostanoid-induced changes to renal function in horses and indicated that COX-2–preferential agents would be likely to have adverse renal effects similar to those for nonselective COX inhibitors in volume-depleted horses.

Contributor Notes

Presented in abstract form at the American College of Veterinary Internal Medicine Forum, New Orleans, June 2012.

The authors thank Kate Burnheim and Rhys Duncan for technical assistance and Kristie Hann for assistance with measurement of creatinine concentrations.

Address correspondence to Dr. Raidal (sraidal@csu.edu.au).
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