Phenylbutazone kinetics and metabolite concentrations in the horse after five days of administration.

Phenylbutazone (PBZ) was administered (8.8 mg/kg of body weight) every 24 hours for 5 consecutive days, orally for the first 4 days and IV on day 5. The half-life (t 1/2) after this daily administration was 6.2 hours and the volume of distribution was 0.152 +/- 0.014 L/kg; the bioavailability after oral administration was 91.8 +/- 2.5%. The plasma concentration of PBZ at experimental hour (EH) 24 (24 hours after the 1st oral dose) was 1.7 +/- 0.39 micrograms/ml and increased to 4.2 +/- 0.29 micrograms/ml at EH 48 (24 hours after the 2nd oral dose). Values at EH 72, 96, and 120 (24 hours after administration of oral doses 3 and 4, and IV dose 5, respectively) were 4.8 +/- 0.62 micrograms/ml, 5.3 +/- 0.84 micrograms/ml, and 4.3 +/- 1.1 micrograms/ml, respectively. Significant increases (P less than 0.05) were measured between EH 24 and 48 with no changes during the subsequent 3 days. Changes in the urinary concentrations of PBZ were not seen over the 5-day dosing period. There were increases in the metabolites oxyphenbutazone and the alpha-alcohol during the 5-day dosing period. There was a delay in the appearance of alpha-alcohol in urine after oral and IV administration.