title: Pharmacokinetics and bioequivalence of two suxibuzone oral dosage forms in horses.
abstract: A disposition and bioequivalence study with a suxibuzone granulated and a suxibuzone paste oral formulation was performed in horses. Suxibuzone (SBZ) is a nonsteroidal anti-inflammatory drug, which was administered to horses (n = 6) at a dosage of 19 mg/kg bwt by the oral route (p.o.) in a two period cross-over design. Suxibuzone is very rapidly transformed into its main active metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ). Therefore plasma and synovial fluid concentrations of SBZ, PBZ and OPBZ were simultaneously measured by a sensitive and specific high-performance liquid chromatographic method. The pharmacokinetic parameters were determined by noncompartmental analysis. Suxibuzone could not be detected in any plasma and synovial fluid samples (< 0.04 microgram/mL). Plasma PBZ and OPBZ concentrations were detected between 30 min and 72 h after granulate and paste administration. Mean plasma concentration of PBZ peaked at 5 h (34.5 +/- 6.7 micrograms/mL) and at 7 h (38.8 +/- 8.4 micrograms/mL), and mean area under the concentration-time curve (AUC0-->LOQ) was 608.0 +/- 162.2 micrograms.h/mL and 656.6 +/- 149.7 micrograms.h/mL after granulate and paste administration, respectively. Mean plasma concentration of OPBZ increased to 5-6.7 micrograms/mL, with the maximum concentration (Cmax) appearing between 9 and 12 h after administration of both formulations. The AUCs0-->LOQ for OPBZ were also similar (141.8 +/- 48.3 micrograms.h/mL granulate vs. 171.4 +/- 45.0 micrograms.h/mL paste). It was concluded that the suxibuzone products were bioequivalent with respect to PBZ. For OPBZ, the 95% confidence intervals of the pharmacokinetic parameters were within the acceptable range of 80-125%. The paste formulation provided greater bioavailability of PBZ and OPBZ.
authors.affiliation: Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Jaraiz
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez
authors.forename: M D
authors.initials: MD
authors.lastname: San Andres
authors.forename: F
authors.initials: F
authors.lastname: Gonzalez
authors.forename: M I
authors.initials: MI
authors.lastname: San Andres
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D004304:Dosage Forms; D006736:Horses / Q000378:metabolism*; D008297:Male; D010653:Phenylbutazone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004304:Dosage Forms; C003371:suxibuzone; D010653:Phenylbutazone