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.
Objective—To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies
Animals—8 IR ponies
Procedures—Metformin (30 mg/kg) was administered to 8 ponies via nasogastric tube Blood samples were collected at intervals for 24 hours. Plasma concentrations of metformin were measured via liquid chromatography-electrospray tandem mass spectroscopy Pharmacokinetic variables were determined via noncompartmental analysis. Metformin (15 mg/kg, PO, twice daily [8 am and 5 pm]) was administered to 4 ponies for an additional 20 days, and blood samples were obtained every 2 days. Plasma concentration at steady state (Css) was determined.
Results—Mean ± SD elimination half-life (t1/2) of metformin was 11.7 ± 5.2 hours, maxima plasma concentration was 748 ± 269 ng/mL at 54 ± 32 minutes, mean area under the curve was 355 ± 92μg•h/mL, and apparent clearance was 90.6 ± 28.1 mL/min/kg. The Css was 122 ± 22 ng/mL.
Conclusions and Clinical Relevance—Metformin reportedly enhances insulin sensitivity of peripheral tissues without stimulating insulin secretion, but bioavailability in horses is low. The t1/2 of metformin in IR ponies was similar to that in humans. Actual clearance of metformin adjusted for bioavailability in IR ponies was similar to that in humans; however, during chronic oral administration at dosages reported in efficacy studies, the Css of metformin was less than values associated with therapeutic efficacy in humans The apparent lack of long-term efficacy of metformin in horses is likely attributable to low bioavailability, rather than to rapid clearance. (Am J Vet Res 2010;71:1201-1206)