Oral administration of tepoxalin in the horse: A PK/PD study

Tepoxalin is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory, and antipyretic 23 properties and has been recently introduced into veterinary medicine. The aim of this study was to eval- 24 uate the pharmacokinetic/pharmacodynamic (PK/PD) profile of tepoxalin to assess whether it would be 25 suitable for clinical use in horses. 26 Six female fasting/fed horses were given 10 mg/kg tepoxalin orally in a cross-over study. After admin- 27 istration, tepoxalin underwent rapid and extensive hydrolytic conversion to its carboxylic acidmetabolite 28 RWJ-20142. In animals that had been fed, the plasma concentrations of tepoxalin were undetectable, 29 whereas in fasting animals they were close to the limit of quantification of the method. No differences 30 between the fasting/fed groups in RWJ-20142 plasma concentrations were shown. Tepoxalin showed a 31 strong and long-lasting ex vivo inhibitory activity against cyclooxygenase (COX)-1, mainly due to itsmain 32 metabolite RWJ-20142. Tepoxalin and RWJ-20142 do not seem to possess either COX-2 or 5-lipoxygenase 33 inhibitory activity in the horse. These features suggest that the drug is a selective COX-1 inhibitor in 34 horses, with no significant anti-inflammatory activity. Thus, its long term use in equine practice could 35 be of concern.