THE DISPOSITION OF SUXIBUZONE IN THE HORSE

A high performance liquid chromatographic method is described to deter mine the anti-inflammatory drug suxibuzone (SXB) and its major metabol ites phenylbutazone (PBZ) and oxyphenbutazone (OPBZ) in equine plasma and urine. When suxibuzone (6 mg/kg) was administered intravenously (i .v.) or orally (p.o.) no parent drug was detected in plasma or in urin e. The disposition of the metabolite PBZ (i.v.) could be described by a 2 compartment model with a beta half-life varying from 7.40 to 8.35 h. Due to severe side effects the use of i.v. suxibuzone should not be encouraged in the horse. PBZ and OPBZ were detected in plasma and uri ne after p.o. SXB administration. Peak plasma PBZ concentrations (8.8 +/- 3.0 mug/ml) occurred 6 h after oral dosing and the terminal expone ntial constant was 0.11 +/- 0.01 h-1. Phenylbutazone and oxyphenbutazo ne were detectable in urine (> 1 mug/ml) for at least 36 h, after p.o. administration. SXB was not hydrolyzed in vitro by horse plasma. Equi ne liver homogenates however appeared to have a very high capacity for hydrolysing SXB, indicating that first-pass effect could be responsib le for the rapid disappearance of this NSAID in the horse.