Pharmacokinetics of transdermal flunixin meglumine and effects on biomarkers of inflammation in horses

Abstract

Flunixin meglumine is a highly efficacious nonsteroidal anti‐inflammatory drug commonly used in equine medicine and especially in performance horses. Recently, a new transdermal flunixin meglumine product has been approved for use in cattle. Although not currently approved for use in the horse, the convenience of this product may prove appealing for use in horses, warranting study. Six horses were administered a single transdermal dose of 500 mg and blood and urine samples collected for up to 96 h post‐administration. Serum for determination of thromboxane concentrations and whole blood samples was collected at various time and challenged with lipopolysaccharide, calcium ionophore, or methanol to induce ex vivo synthesis of eicosanoids. Concentrations of flunixin, 5‐OH flunixin, and eicosanoids were measured using LC‐MS/MS and non‐compartmental pharmacokinetic analysis performed on concentration data. Serum concentrations of flunixin and 5‐OH flunixin were above the limit of quantitation at 96 h post‐administration in both serum and urine. The mean (range) for Cmax, Tmax and the terminal half‐life were 515.6 (369.7–714.0) ng/ml, 8.67 (8.0 12.0) h, and 22.4 (18.3–42.5) h, respectively. Following transdermal administration, based on effects on eicosanoid synthesis, flunixin meglumine inhibited cyclooxygenase 1 and 2 and 15‐lipooxygenase activity, with anti‐inflammatory effects lasting for 24–72 h.

Non‐steroidal anti‐inflammatory drugs in equine orthopaedics

“… 19 , 20 Recently, a study has evaluated the pharmacokinetics of a bovine transdermal formulation of flunixin meglumine in horses. 21 In this study, transdermal administration (500 mg) was well tolerated in horses with no adverse effects noted. The maximum systemic concentration of flunixin meglumine was lower and the time to maximum absorption was longer than reported for oral and intramuscular administration; however, inhibition of COX‐1 and COX‐2 was identified for 24‐72 hours post administration.…”

“…Injectable flunixin meglumine is labelled for intravenous or intramuscular injection; however, intramuscular administration should be avoided due to the risk of development of clostridial myonecrosis 19‐20 . Recently, a study has evaluated the pharmacokinetics of a bovine transdermal formulation of flunixin meglumine in horses 21 . In this study, transdermal administration (500 mg) was well tolerated in horses with no adverse effects noted.…”

“…The maximum systemic concentration of flunixin meglumine was lower and the time to maximum absorption was longer than reported for oral and intramuscular administration; however, inhibition of COX‐1 and COX‐2 was identified for 24‐72 hours post administration. 21 …”

“…The maximum systemic concentration of flunixin meglumine was lower and the time to maximum absorption was longer than reported for oral and intramuscular administration; however, inhibition of COX-1 and COX-2 was identified for 24-72 hours post administration. 21 Although phenylbutazone is more commonly used in cases of orthopaedic pain and disease, flunixin meglumine is also effective in decreasing lameness. A study examining doses of flunixin meglumine at 0.5, 1.1 and 2.2 mg/kg in horses with experimentally induced lameness found decreases in heart rate and lameness scores with all treatment groups.…”

Pharmacokinetic Evaluation of a Novel Transdermal Ketoprofen Formulation in Healthy Dogs

“…Only a few studies have reported successful transdermal delivery of NSAIDs in animals, including ketoprofen in cattle [ 26 ] and pigs [ 27 ], and flunixin meglumine in horses [ 28 ], goats [ 29 ], and piglets [ 30 ]. Some studies targeted local penetration only, including naproxen [ 31 ], methyl salicylate [ 32 ], meloxicam [ 33 ], and celecoxib [ 34 ].…”