AASRP Research Summary

Pharmacokinetics of intravenous and transdermal flunixin meglumine in wool and hair sheep (Ovis aries)

Date/Time: 9/12/2025    16:45
Author: Danielle A Mzyk
Clinic: North Carolina State University College of Veterinary Medicine
City, State, ZIP: Raleigh, NC  27607

Danielle A. Mzyk, DVM, PhD 1 ; Kaitlyn G. Forrest, BS 1 ; Jennifer L. Halleran, DVM, PhD, DACVIM 1 ; Ronald E. Baynes, DVM, PhD 1 ;
1Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, NC 27607

Introduction:

Currently there are no drugs approved for the control of pain in sheep in the United States, and very limited pain medications approved for use in food-producing species. A transdermal (TD) formulation of flunixin meglumine has been approved for cattle for control of pain associated with footrot, demonstrating rapid absorption and therapeutic effectiveness. Transdermal route of administration offers a more easily accessible dosing strategy for producers and veterinarians, however, species differences in absorption, distribution, metabolism and elimination must be examined. The bioavailability of flunixin administered in a transdermal formulation has not been evaluated in sheep. The objective of the study was to evaluate pharmacokinetics of flunixin meglumine of intravenous (IV) and transdermal (TD) flunixin meglumine administration on different coat types (wool vs hair) in 12 healthy sheep. The authors hypothesize that hair sheep (katahdins) will have higher systemic bioavailability when compared with wool sheep (dorsets) but similar PK parameters when compared to goats.

Materials and methods:

A dose of 2.2 mg/kg of flunixin meglumine injectable solution was administered IV and 3.3 mg/kg of flunixin meglumine in a transdermal formulation was administered TD using a cross-over design. Plasma samples were obtained for 96 hours following both IV and TD administration, respectively. Flunixin concentrations were quantified by use of high-performance liquid chromatography with mass spectrometry and PK parameters derived using compartmental and population non-linear mixed effect modeling.

Results:

The mean bioavailability of TD flunixin was not significantly different (48.76 ± 17.49 % and 36.61 ± 4.33 %; p = 0.093) in wool and hair sheep, respectively. Maximum plasma concentrations following TD administration were higher (P = 0.008) in wool sheep (1.57 μg/ml; range, 0.6 - 3.41 μg/ml) compared to hair sheep (0.57 μg/ml; range, 0.36 - 0.83 μg/ml). Area under the curve extrapolated to infinity following TD administration (AUC0-inf) was significantly higher (p = 0.002) in wool sheep (27.94 hr x μg/ml; range: 21.8 - 38.3) compared to hair sheep (16.74 hr x μg/ml; range: 13.69 - 20.86). Coat type has a significant effect on absorption rate following TD administration as the mean absorption time was significantly (p = 0.045) decreased in wool sheep (13.74 hrs) than in hair sheep (23.73 hrs).

Significance:

Transdermal formulation of flunixin meglumine administered to wool sheep showed higher exposure and decreased absorption times as compared to wool sheep. The PK results presented provide further support for future clinical studies to examine the efficacy of transdermal flunixin in different breeds of sheep.