Equine anti-doping rules have been established to prevent a horse’s performance being altered after the administration of prohibited substances, including approved drugs used for legitimate treatment. Phenylbutazone (PBZ) is a non-steroidal anti-inflammatory drug (NSAID) widely used in equine veteri- nary medicine for the treatment of conditions associated with Ó 2012 The Authors Journal of Veterinary Pharmacology and Therapeutics Ó 2012 Blackwell Publishing Ltd, J. vet. Pharmacol. Therap. 35 (Suppl. 3), 137–178 pain and inflammation, such as musculoskeletal disorders. PBZ is one of the most frequently identified drugs in the anti-doping controls. Thresholds for PBZ in equine plasma of 15 and 2 lg ml)1 were proposed by United States Equestrian Federa- tion-USEF and Racing commissioner international-RCI. The Federation Equestre Internationale-FEI, through the European Horserace Scientific Liaison Committee-EHSLC, has proposed a detection time of 168 h for PBZ in blood based on a LOD of 0.050 lg ml)1. The aim of this study was to evaluate plasma clearance of PBZ in healthy horses following both intravenous and oral administration of two commercial products marketed in Italy at the maximum dosage regimen, recommended by the manufacturer. MATERIALS AND METHODS PBZ was administered to horses intravenously (n = 6) or orally (n=6) at a dose rate of 4.4mgkg)1 once daily for five consecutive days. Both experiments involved six thoroughbred horses (three females and three males) weighing from 450 to 600 kg and aged 5–11 years. Blood (10 ml) samples were collected before the last dose (t0) and then after 1, 3, 6, 9, 12 and 24 h; and every 12 h for 10 days after treatment. Plasma levels of PBZ and its major metabolite OPBZ were measured by HPLC-UV (LOD = 0.025 lg ml)1). The study was conducted with the approval of the ethic committee of the University of Pisa. RESULTS Plasma PBZ and OPBZ concentrations, after both intravenous and oral administration, showed a rapid elimination profile and were below the LOD at 84 h after the administration of the last dose. Plasma levels of OPBZ were 25% or less of the concentra- tions of PBZ, showing a rapid elimination profile and being less than LOD at 84 h after the administration of the last dose. At 168 h both plasma PBZ and OPBZ were not detectable in any horse. The oral bioavailability of PBZ was 23%. CONCLUSIONS Plasma elimination profile of the two commercial formulations of PBZ investigated in this study was rapid. The detection time suggested by the FEI for PBZ is largely protective. The thresholds indicated by USEF were reached within 4–6 h after intravenous administration and have never been reached after oral admin- istration. The thresholds set by RCI were reached within 20 h both after intravenous and oral administration.
Detection time of two commercial forms of phenylbutazone in the horse
MEUCCI, VALENTINA;SGORBINI, MICAELA;INTORRE, LUIGI
2012-01-01
Abstract
Equine anti-doping rules have been established to prevent a horse’s performance being altered after the administration of prohibited substances, including approved drugs used for legitimate treatment. Phenylbutazone (PBZ) is a non-steroidal anti-inflammatory drug (NSAID) widely used in equine veteri- nary medicine for the treatment of conditions associated with Ó 2012 The Authors Journal of Veterinary Pharmacology and Therapeutics Ó 2012 Blackwell Publishing Ltd, J. vet. Pharmacol. Therap. 35 (Suppl. 3), 137–178 pain and inflammation, such as musculoskeletal disorders. PBZ is one of the most frequently identified drugs in the anti-doping controls. Thresholds for PBZ in equine plasma of 15 and 2 lg ml)1 were proposed by United States Equestrian Federa- tion-USEF and Racing commissioner international-RCI. The Federation Equestre Internationale-FEI, through the European Horserace Scientific Liaison Committee-EHSLC, has proposed a detection time of 168 h for PBZ in blood based on a LOD of 0.050 lg ml)1. The aim of this study was to evaluate plasma clearance of PBZ in healthy horses following both intravenous and oral administration of two commercial products marketed in Italy at the maximum dosage regimen, recommended by the manufacturer. MATERIALS AND METHODS PBZ was administered to horses intravenously (n = 6) or orally (n=6) at a dose rate of 4.4mgkg)1 once daily for five consecutive days. Both experiments involved six thoroughbred horses (three females and three males) weighing from 450 to 600 kg and aged 5–11 years. Blood (10 ml) samples were collected before the last dose (t0) and then after 1, 3, 6, 9, 12 and 24 h; and every 12 h for 10 days after treatment. Plasma levels of PBZ and its major metabolite OPBZ were measured by HPLC-UV (LOD = 0.025 lg ml)1). The study was conducted with the approval of the ethic committee of the University of Pisa. RESULTS Plasma PBZ and OPBZ concentrations, after both intravenous and oral administration, showed a rapid elimination profile and were below the LOD at 84 h after the administration of the last dose. Plasma levels of OPBZ were 25% or less of the concentra- tions of PBZ, showing a rapid elimination profile and being less than LOD at 84 h after the administration of the last dose. At 168 h both plasma PBZ and OPBZ were not detectable in any horse. The oral bioavailability of PBZ was 23%. CONCLUSIONS Plasma elimination profile of the two commercial formulations of PBZ investigated in this study was rapid. The detection time suggested by the FEI for PBZ is largely protective. The thresholds indicated by USEF were reached within 4–6 h after intravenous administration and have never been reached after oral admin- istration. The thresholds set by RCI were reached within 20 h both after intravenous and oral administration.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
