Pharmacokinetics, metabolism and excretion of phenylbutazone in cattle following intravenous, intramuscular and oral administration

The plasma concentrations of phenylbutazone (PBZ) and its major metabolites, oxyphenbutazone (OPBZ) and gamma-OH-phenylbutazone (OHPBZ) were determined for up to 72 h in six horses, following intravenous (i.v.) and intramuscular (i.m.) administration of 4 g phenylbutazone, 20 ml Phenylarthrite Ventoquinol (Vetoquinol Spécialités Pharmaceutiques Vétérinaires, Magny-Vernois, 70200 Lure, France). After i.v. dosing the plasma disposition was best described by a two-compartment open model. The hydroxylated metabolites OPBZ and OHPBZ were present in detectable concentrations for 72 h and 48 h, respectively. After 36 h the OPBZ concentrations exceeded plasma PBZ concentrations. The plasma disposition following i.m. injection could be described by a one-compartment open model. The hydroxylated metabolites OPBZ and OHPBZ were present in detectable concentrations for 72 h and 36 h, respectively. Only after 72 h was the concentration of OPBZ in plasma higher than the concentration of PBZ. The mean i.m. bioavailability of phenylbutazone was calculated to be 91.7 +/- 10.1%.

Section: Discussionsupporting

confidence: 93%

The intramuscular bioavailability of a phenylbutazone preparation in the horse

Landuyt

Delbeke

Debackere

1993

“…The slow elimination of PBZ has been reported previously in ruminant species. Lees et al . (1988) administered PBZ i.v.…”

Section: Discussionmentioning

confidence: 99%

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

Cheng

McKeller

Nolan

1998

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.

“…The two most common metabolites of phenylbutazone, oxyphenbutazone and hydroxphenylbutazone, were not present in any significant amounts (data not shown). This supports previous reports that demonstrate that this drug undergoes relatively limited and slow biotransformation in cattle (Martin et al ., 1984; Lees et al ., 1988). Phenylbutazone pharmacokinetic parameters as determined from plasma are presented in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics of phenylbutazone in beef steers

Veau

Pedersoli

Cullison

et al. 2002

Phenylbutazone was administered intravenously to a group of 11 beef steers at a dosage of 6 mg/kg of body weight. Whole plasma and protein-free plasma were analyzed for phenylbutazone residues. Pharmacokinetic parameters of total and free phenylbutazone in plasma were calculated using a noncompartmental method. In regards to whole plasma data, the mean volume of distribution at steady state (Vss), was 140 mL/kg body weight, with a mean (+/-SEM) terminal elimination half-life (t1/2) of 34 +/- 9 h. The mean clearance was 3.2 mL/h/kg body weight. The Vss, as determined from the protein-free plasma fraction, was 54093 mL/kg body weight. This larger Vss of free phenylbutazone compared with total plasma phenylbutazone was attributed to a high degree of plasma protein binding, as well as the greater penetration of free phenylbutazone into tissues. The mean t1/2 of free phenylbutazone was 35 +/- 12 h. This similarity to the t1/2 estimated from total plasma phenylbutazone data is attributed to an equilibrium between free and plasma phenylbutazone during the terminal elimination phase. The pharmacokinetic parameters of free and total plasma phenylbutazone in beef steers are statistically similar to those previously reported for lactating dairy cows.