PHENYLBUTAZONE KINETICS AND METABOLITE CONCENTRATIONS IN THE HORSE AFTER 5 DAYS OF ADMINISTRATION

Abstract

Phenylbutazone (PBZ) was administered (8.8 mg/kg body wt) every 24 h for 5 consecutive days, orally for the first 4 days and i.v. on day 5. Half-life (t1/2) after this daily administration was 6.2 h and volume of distribution was 0.152 .+-. 0.014 l/kg; bioavailability after oral administration was 91.8 .+-. 2.5%. The plasma concentration of PBZ at experimental hour (EH) 24 (24 h after the 1st oral dose) was 1.7 .+-. 0.39 .mu.g/ml and increased to 4.2 .+-. 0.29 .mu.g/ml at EH 48 (24 h after the 2nd oral dose). Values at EH 72, 96 and 120 (24 h after administration of oral doses 3 and 4, and i.v. dose 5, respectively) were 4.8 .+-. 0.62, 5.3 .+-. 0.84 and 4.3 .+-. 1.1 .mu.g/ml, respectively. Significant increases (P < 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 i.v. administration.