Pharmacokinetic studies of flunixin meglumine and phenylbutazone in plasma, exudate and transudate in sheep

Abstract

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 sheep prepared with subcutaneous (s.c.) tissue-cages in which an acute inflammatory reaction was stimulated with carrageenan. Pharmacokinetics of 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 (t1/2beta) of 2.48 +/- 0.12 h and an area under the concentration - time curve (AUC) of 30.61 +/- 3.41 Lg/mL x h. Elimination of PBZ from plasma was slow (t1/2beta = 17.92 +/- 1.74 h, AUC = 968.04 +/- microg/mL x h). Both FM and PBZ distributed well into exudate and transudate although penetration was slow, indicated by maximal drug concentration (Cmax) for FM of 1.82 +/- 0.22 microg/mL at 5.50 +/- 0.73 h (exudate) and 1.58 +/- 0.30 microg/mL at 8.00 h (transudate), and Cmax for PBZ of 22.32 +/- 1.29 microg/mL at 9.50 +/- 0.73 h (exudate) and 22.07 +/- 1.57 microg/mL at 11.50 +/- 1.92 h (transudate), and a high mean tissue-cage fluids:plasma AUClast ratio obtained in the FM and PBZ groups (80-98%). These values are higher than previous reports in horses and calves using the same or higher dose rates. Elimination of FM and PBZ from exudate and transudate was slower than from plasma. Consequently the drug concentrations in plasma were initially higher and subsequently lower than in exudate and transudate.

Development of a facial expression scale using footrot and mastitis as models of pain in sheep

“…However, they did not find any effect of NSAIDs on time to recovery when compared with sheep that only received an antibiotic. In sheep, meloxicam has a longer elimination half-life than flunixin meglumine (10.85 ± 1.21 h, 2.48 ± 0.12 h respectively) (Cheng et al, 1998;Shukla et al, 2007) and is detectable in blood plasma for up to 72 hours (Shukla et al, 2007) compared to 32 hours for flunixin meglumine (Cheng et al, 1998). These studies provide evidence for meloxicam to be a better alternative to flunixin meglumine in reducing inflammation and pain associated with diseases such as footrot and mastitis in sheep.…”

Pharmacokinetics of Flunixin after Intravenous Administration in Healthy and Endotoxaemic Rabbits

“…administration to rabbits, as well as those reported in rabbits (Miyazaki et al, 2001;Elmas et al, 2005), sheep (Cheng et al, 1998a), camels (Was¢ et al, 1998) and broilers (Baert and De Backer, 2002), were best described using a two-compartment open model.…”

“…Characterization of the pharmacokinetics of FM have been established in healthy animals of most species (McKellar et al, 1989;Landoni et al, 1995a;Cheng et al, 1998a;Was¢ et al, 1998;De Backer, 2002, 2003) and in healthy rabbits (Miyazaki et al, 2001;Elmas et al, 2005). On the other hand, few articles are available on the pharmacokinetics of FM in diseased animals (Toutain et al, 1994;Rantala et al, 2002).…”

Pharmacokinetics and Pharmacodynamic Effects of Flunixin after Intravenous, Intramuscular and Oral Administration to Dairy Goats

“…[1,19,13]) and its pharmacokinetic properties has been studied in cattle [8,12], sheep [18,2], camels [14,16] and llamas [9]. …”