Concentrations of indomethacin and its metabolite desmethylindomethacin in plasma and urine after repeated indomethacin topical application to Thoroughbreds.
Authors: Kusano K, Minamijima Y, Mashita S, Kunii H, Yamashita S, Nagata S
Journal: Equine veterinary journal
Summary
# Editorial Summary: Topical Indomethacin Pharmacokinetics in Thoroughbreds Despite widespread use of topical indomethacin cream in Japanese racing yards, its systemic absorption and elimination kinetics remained undocumented—a concerning gap given that NSAIDs are subject to strict racing regulations and withdrawal periods. Kusano and colleagues administered 500 mg of indomethacin (via 50 g of 1% cream) to seven Thoroughbred mares over the back and hips for three consecutive days, then tracked both the parent drug and its primary metabolite (desmethylindomethacin) in plasma and urine using liquid chromatography-mass spectrometry. The drug remained detectable in plasma for up to 72 hours post-final application and in urine for 96 hours, whilst the metabolite persisted in urine for up to 96 hours—substantially longer than many practitioners might assume from a topical formulation. Based on detection thresholds, the authors estimated a withdrawal period of approximately 342 hours (14 days), which is considerably longer than the local anti-inflammatory effects practitioners typically expect. For farriers, vets and trainers involved with racing or competition horses, this research underscores that topical NSAIDs achieve meaningful systemic exposure and should be managed with the same regulatory vigilance as systemic administration; the extended urinary detection window also suggests that indomethacin serves as a reliable marker compound for doping control testing.
Read the full abstract on PubMed
Practical Takeaways
- •Topical indomethacin persists systemically in racehorses for up to 96 hours in urine and should be considered a banned substance with a 342-hour withdrawal time before competition testing
- •Veterinarians and trainers in racing jurisdictions with drug testing should be aware that topical indomethacin application commonly used in Japanese racing remains detectable for approximately 2 weeks
- •Urine testing is more sensitive than plasma for detecting indomethacin residues, making it the preferred matrix for regulatory compliance and doping control
Key Findings
- •Indomethacin was quantifiable in plasma up to 48-72 hours and in urine up to 96 hours after final topical application of 500 mg per horse
- •Desmethylindomethacin (active metabolite) was quantifiable in plasma up to 48 hours and urine up to 72-96 hours post-application
- •Estimated withdrawal time based on limit of detection was 342 hours (approximately 14 days)
- •Hydrolysis of urine samples with hydrochloric acid was effective for detecting indomethacin and its metabolite, supporting use as a doping test marker