Pharmacokinetics and bioequivalence of two suxibuzone oral dosage forms inhorses

A disposition and bioequivalence study with a suxibuzone granulated and a s uxibuzone 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 perio d cross-over design. Suxibuzone is very rapidly transformed into its main a ctive metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ). Therefo re plasma and synovial fluid concentrations of SBZ, PBZ and OPBZ were simul taneously measured by a sensitive and specific high-performance liquid chro matographic method. The pharmacokinetic parameters were determined by nonco mpartmental analysis. Suxibuzone could not be detected in any plasma and sy novial fluid samples (< 0.04 mu g/mL). Plasma PBZ and OPBZ concentrations w ere detected between 30 min and 72 h after granulate and paste administrati on. Mean plasma concentration of PBZ peaked at 5 h (34.5 +/- 6.7 mu g/mL) a nd at 7 h (38.8 +/- 8.4 mu g/mL), and mean area under the concentration-tim e curve (AUC(0-->LOQ)) was 608.0 +/- 162.2 mu g.h/mL and 656.6 +/- 149.7 mu g.h/mL after granulate and paste administration, respectively. Mean plasma concentration of OPBZ increased to 5-6.7 mu g/mL, with the maximum concent ration (C-max) appearing between 9 and 12 h after administration of both fo rmulations. The AUCs(0-->LOQ) for OPBZ were also similar (141.8 +/- 48.3 mu g.h/mL granulate vs. 171.4 +/- 45.0 mu g.h/mL paste). It was concluded tha t 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 bi oavailability of PBZ and OPBZ.