Phenylbutazone toxicity in ponies.

This study found that giving ponies relatively high, repeated doses of the pain reliever phenylbutazone caused serious side effects, including protein loss, fluid shifts, intestinal swelling, and in some cases death. The work highlights that ponies are especially sensitive and that both dose and duration matter, even when the drug is given intravenously.

What the researchers did

• Administered phenylbutazone orally to eight ponies at approximately 10 mg/kg/day for 7–14 days.
• Monitored for clinical signs and ran blood biochemistry during treatment.
• Performed necropsies on ponies that died to identify pathological changes.
• Conducted a small follow-up in two ponies receiving intravenous phenylbutazone at 4.0 mg/kg daily for 7 days to compare effects by route and dose.

Key findings

• Seven of eight orally treated ponies developed toxicity signs within 1–2 weeks.
• Clinical signs included anorexia (reduced appetite), depression, and abdominal (ventral) edema.
• Biochemistry showed:
  • Decreased total plasma protein (TP), indicating protein loss and/or dilution.
  • Decreased calcium, consistent with reduced protein (albumin-bound calcium falls when albumin drops).
  • Increased blood urea, suggesting altered renal perfusion/function and/or catabolism; the authors interpreted the overall pattern as compatible with water retention.
• Three ponies died during treatment after developing shock.
• Necropsy revealed submucosal edema of the large intestine and oral ulceration in affected animals.
• With intravenous dosing at 4.0 mg/kg for 7 days, one of two ponies developed a marked fall in total plasma protein, showing risk even at lower dose via IV over a week.

How to interpret the clinical and laboratory changes

• Ventral/abdominal edema plus low total protein point toward a protein-losing enteropathy and reduced oncotic pressure, allowing fluid to leak into tissues.
• Low calcium is likely secondary to hypoalbuminemia (total calcium falls when albumin falls), not necessarily true ionized hypocalcemia.
• Elevated urea can reflect decreased renal blood flow from NSAID-induced prostaglandin inhibition, prerenal azotemia from fluid shifts, or increased protein catabolism; concurrent water/sodium retention can also raise urea concentration.
• Oral ulceration indicates mucosal injury, either from local contact irritation or systemic mucosal compromise.

Proposed mechanism of toxicity

• Phenylbutazone is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase and reduces prostaglandin synthesis.
• In the gastrointestinal tract, prostaglandins support mucosal blood flow and barrier integrity; their suppression predisposes to colonic injury, edema, and protein loss.
• Loss of plasma proteins lowers oncotic pressure, driving third-spacing of fluid (edema) and potentially reducing circulating volume.
• Reduced effective circulating volume, compounded by NSAID-related renal vasoconstriction, can precipitate shock, which the authors linked to the observed submucosal colonic edema.

Oral versus intravenous dosing insights

• Oral dosing at ~10 mg/kg/day for 7–14 days was clearly toxic for most ponies in this series.
• Intravenous dosing at 4 mg/kg/day for 7 days still produced a major drop in plasma protein in one of two ponies, indicating:
  • Systemic toxicity is not solely due to local gastrointestinal contact; route does not eliminate risk.
  • Duration of administration is a key driver of adverse effects, even at lower doses.

Clinical implications

• Ponies appear particularly susceptible to phenylbutazone toxicity; high daily doses and multi-day courses greatly increase risk.
• Typical modern equine dosing is substantially lower than 10 mg/kg/day; exceeding recommended dose or duration should be avoided, especially in ponies.
• Monitor animals on multi-day NSAIDs for:
  • Decreased appetite, depression, colic signs, diarrhea, ventral edema, and oral lesions.
  • Laboratory markers: total protein/albumin, calcium, urea and creatinine, packed cell volume/total solids.
• At the first evidence of hypoproteinemia or edema, reassess therapy and supportive care to prevent progression to shock.
• Avoid concurrent NSAIDs or corticosteroids, ensure adequate hydration, and consider alternative analgesics with caution and appropriate monitoring.

Limitations and context

• Small sample size and lack of a contemporaneous control group limit precision of risk estimates.
• Dose used for oral administration was high relative to common current practice, so findings define a clear toxicity threshold rather than routine outcomes.
• Pathology descriptions emphasize edema but may not capture the full spectrum of NSAID-associated large colon disease.

How this fits with current knowledge

• The pattern described—hypoproteinemia, ventral edema, colonic wall edema, and oral ulceration—is consistent with NSAID-associated large colon injury (often termed right dorsal colitis in horses) and protein-losing enteropathy.
• Findings reinforce the importance of species and size-specific dosing, duration limits, and laboratory monitoring when using phenylbutazone in equids, with particular caution in ponies.