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  • Author or Editor: Shawnee R. Montgomery x
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Abstract

OBJECTIVE

To examine the pharmacokinetics and ex vivo pharmacodynamics of oral firocoxib administration in New Zealand White rabbits (Oryctolagus cuniculus).

ANIMALS

6 healthy New Zealand White rabbits.

PROCEDURES

Pharmacokinetics were determined from plasma concentrations measured via ultra performance liquid chromatography-tandem mass spectrometry after oral administration of firocoxib at a dose of 3.74 to 4.20 mg/kg. Pharmacokinetic analysis was performed using non compartmental methods. Pharmacodynamics of firocoxib were evaluated by measuring plasma concentrations of thromboxane and prostaglandin via ELISAs as surrogate markers of cyclooxygenase enzyme isoform inhibition.

RESULTS

The terminal rate constant was 0.07 hours (range, 0.05 to 0.11 h). The mean maximum concentration (Cmax) and time to Cmax were 0.16 µg/mL and 3.81 hours (range, 2.0 to 8.0 h), respectively. Mean residence time was 15.02 hours. Mean elimination half-life was 9.12 hours. For the pharmacodynamic analysis, firocoxib administration did not demonstrate a significant difference between any time point for prostaglandin E2 and only a significant difference between 24 and 48 hours for thromboxane B2.

CLINICAL RELEVANCE

Although the pharmacokinetic research supports that plasma firocoxib concentrations that would be therapeutic in dogs are achieved in rabbits, the pharmacodynamic results do not demonstrate a significant difference in levels of cyclooxygenase-2 inhibition, which indirectly reflects the anti-inflammatory effects of the drug. Further pharmacodynamic studies and multidose studies are warranted to determine the efficacy and safety of this drug in rabbits.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To assess the effects of transdermal flunixin administration on serum prostaglandin E2 (PGE2) and cortisol concentrations in piglets undergoing castration.

ANIMALS

104 litters with at least 4 male piglets/litter.

PROCEDURES

Litters were randomly assigned to 1 of 4 treatments: transdermal flunixin (3.33 mg/kg) administration followed by surgical castration (CF; n = 28), transdermal flunixin administration followed by sham castration (SF; n = 26), application of physiologic saline solution followed by sham castration (S; n = 26), and application of physiologic saline solution followed by surgical castration (C; n = 24). Blood samples were collected 24 hours before and 1, 4, and 25 hours after castration or sham castration.

RESULTS

Serum PGE2 concentrations for piglets in the C and CF groups did not differ at any time. Piglets in the S group tended to have higher serum PGE2 concentrations 1 hour after sham castration compared with piglets in the SF group. One hour after the procedure, piglets that underwent castration had higher serum cortisol concentrations than did piglets that underwent sham castration. Piglets in the CF group had higher serum cortisol concentrations than did piglets in the SF group 4 hours after the procedure, but serum cortisol concentrations did not differ between the C and S groups.

CLINICAL RELEVANCE

Further studies are needed to explore dosing regimens, including effective doses and administration frequencies, and the pharmacokinetics of flunixin following transdermal administration in piglets undergoing castration.

Open access
in American Journal of Veterinary Research