PHARMACOKINETIC STUDIES OF FLUNIXIN MEGLUMINE AND PHENYLBUTAZONE IN PLASMA, EXUDATE AND TRANSUDATE IN SHEEP

Flunixin meglumine (FM, 1.1 mg/kg) and phenylbutazone (PBZ, 4.4 mg/kg) were administered intravenously (i.v.) as a single dose to eight shee p prepared with subcutaneous (s.c.) tissue-cages in which an acute inf lammatory reaction was stimulated with carrageenan. Pharmacokinetics o f FM, PBZ and its active metabolite oxyphenbutazone (OPBZ) in plasma, exudate and transudate were investigated. Plasma kinetics showed that FM had an elimination half-life (t(1/2 beta)) of 2.48 +/- 0.12 h and a n area under the concentration - time curve (AUC) of 30.61 +/- 3.41 mu g/mL.h. Elimination of PBZ from plasma was slow (t(1/2 beta) = 17.92 +/- 1.74 h, AUC = 968.04 +/- mu g/mL.h.). Both FM and PBZ distributed well into exudate and transudate although penetration was slow, indica ted by maximal drug concentration (C-max) for FM of 1.82 +/- 0.22 mu g /mL at 5.50 +/- 0.73 h (exudate) and 1.58 +/- 0.39 mu g/mL at 8.00 h ( transudate), and C-max for PBZ of 22.32 +/- 1.29 mu g/mL at 9.50 +/- 0 .73 h (exudate) and 22.07 +/- 1.57 mu g/mL at 11.50 +/- 1.92 h (transu date), and a high mean tissue-cage fluids:plasma AUC(last) ratio obtai ned in the FM and PBZ groups (80-98%). These values are higher than pr evious reports in horses and calves using the same or higher dose rate s. Elimination of FM and PBZ from exudate and transudate was slower th an from plasma. Consequently the drug concentrations in plasma were in itially higher and subsequently lower than in exudate and transudate.