Synopsis of what is known about firocoxib in horses

Of particular note is the recommendation of a single loading dose of 0.3 mg/kg in order to achieve the recommended steady state within 24 hrs. Some clinicians have found that firocoxib, started at regular doses, does not perform well for the first few days on acute inflammation and pain. Pharmokintecis explain why. The long half-life that makes once-daily dosing possible also has been used to recommend a lower dose so as not to build up toxic amounts over time. When the higher loading dose is used once, firocoxib was found to be at least as effective, and more effective for some symptoms, as phenylbutazone. There is a clinical impression that firocoxib is safer than the other NSAIDs available for horses.
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Synopsis of the pharmacokinetics, pharmacodynamics, applications, and safety of firocoxib in horses
Vet Anim Sci. 2023 Jan 11;19:100286.
Authors
Charbel Fadel 1 , Mario Giorgi 1 2
Affiliations

1 Department of Veterinary Medicine, University of Sassari, Sassari, Italy.
2 Department of Veterinary Sciences, University of Pisa, Pisa, Italy.

Abstract

According to in vitro and in vivo investigations, firocoxib (FX), a second-generation coxib, is a highly selective COX-2 inhibitor in horses. With a COX-1/COX-2 IC50 ratio of 643 in horses, FX spares the COX-1 inhibitory effects. It is approved for the treatment of musculoskeletal problems and lameness in horses and dogs with osteoarthritis (OA). For the treatment of OA in horses, both an injectable formulation for IV administration at a dose of 0.09 mg/kg for five days and an oral paste formulation at a dose of 0.1 mg/kg for 14 days are licensed. Numerous analytical methods were reported in the literature to quantify FX in biological fluids, using HPLC and LC-MS. FX presents remarkable pharmacokinetics and pharmacodynamics compared to other coxibs. It has an oral bioavailability of 80% or higher and is effectively absorbed by horses. Its volume of distribution is around 2 L/kg, and it is slowly eliminated. Due to the long elimination half-life (around 2 days), which allows a once daily dosing, a single 0.3 mg/kg loading dose has been recommended. This enables the establishment of steady-state drug concentrations within 24 h, making it appropriate for acute treatment as well. Its IC80 is equal to 103 ng/mL in whole blood and, with an EC50 of 27 ng/mL, it has the highest affinity for its receptor compared to the other commonly administered NSAIDs in horses.

Conclusion
In vitro and in vivo studies have demonstrated that FX is a highly selective COX-2 inhibitor. Both an injectable formulation for intravenous administration at a dose of 0.09 mg/kg for five days and an oral paste formulation with a dose of 0.1 mg/kg for 14 days are approved for use in treating OA in horses. A canine tablet formulation is also available, and may be an equally effective anti-inflammatory drug compared to the other formulations. However, the use of the canine formulation is controversial because it is unapproved, yet it is often provided because it is less expensive than the paste. FX is well absorbed in horses, with an oral bioavailability of 80% or more. It is slowly eliminated, and Vd values are around 2 L/kg. Because of the long elimination half-life, which has been reported to be as long as two days, it may take several days to achieve steady concentrations and maximal efficacy. To remedy this, a single 0.3 mg/kg loading dose has been recommended, which allows for the establishment of average steady-state drug concentrations within 24 h, making it suitable for acute treatment as well. It should be noted that FX in neonates displays different pharmacokinetics than in adult horses. After 14 days of dosing in clinical trials on horses with spontaneously occurring OA, the overall clinical efficacy of FX was optimal at the recommended doses.

Keywords: Coxib; Firocoxib; Horses; Pain management; Pharmacodynamics; Pharmacokinetics.