The disposition of suxibuzone in the horse.
A high performance liquid chromatographic method is described to determine the anti-inflammatory drug suxibuzone (SXB) and its major metabolites 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 urine. 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 urine after p.o. SXB administration. Peak plasma PBZ concentrations (8.8 +/- 3.0 micrograms/ml) occurred 6 h after oral dosing and the terminal exponential constant was 0.11 +/- 0.01 h-1. Phenylbutazone and oxyphenbutazone were detectable in urine (> 1 microgram/ml) for at least 36 h, after p.o. administration. SXB was not hydrolyzed in vitro by horse plasma. Equine liver homogenates however appeared to have a very high capacity for hydrolysing SXB, indicating that first-pass effect could be responsible for the rapid disappearance of this NSAID in the horse.
Delbeke
F T
FT
Vakgroep Farmacologie Farmacie en Toxicologie van de Huisdieren, Faculteit Diergeneeskunde, Universiteit Gent, Belgium.
Vynckier
L
L
Debackere
M
M
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D005260:Female; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D010113:Oxyphenbutazone / Q000493:pharmacokinetics; D010653:Phenylbutazone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D011485:Protein Binding
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; C003371:suxibuzone; D010653:Phenylbutazone; D010113:Oxyphenbutazone