If you're fighting tooth and nail to administer oral medications, the introduction of a transdermal option often pleases horses and handlers alike. Transdermal medications are applied to the surface of the skin, typically in the form of an ointment or gel, so as to allow gradual absorption into the body. Are you considering transdermal medications, especially anti-inflammatories? If so, it's important to understand how these drugs are absorbed and eliminated, particularly if your horse is involved in competition and subject to stringent drug withdrawal times.
In the U.S., a transdermal formulation of the nonsteroidal anti-inflammatory (NSAID) diclofenac sodium, sold under the brand name Surpass, is approved for use in horses. Recently, a transdermal product containing flunixin meglumine was approved in cattle and is therefore available for off-label use in horses. Flunixin meglumine is often called by the common brand name Banamine.
To assess how transdermal delivery of flunixin meglumine behaves in the body compared to other routes of administration (e.g., oral, intravenous, intramuscular), researchers applied a 10-mL dose of transdermal flunixin meglumine along the midline of the horse's back, from the withers to the tailhead. This was equivalent to a standard 500-mg dose of flunixin meglumine per horse. *
Blood and urine samples were intermittently collected for up to 96 hours after administration to measure the intricacies of how the medication is absorbed and cleared, a science known as pharmacokinetics.
“Transdermal application was well tolerated in all six study horses, with no horse showing any negative dermal effects,” said Peter Huntington, B.V.Sc., M.A.C.V.Sc., director of nutrition at Kentucky Equine Research.
In terms of the drug's behavior, here's what the research team found:
- The maximum concentration of flunixin meglumine in blood was only an average of 515 ng/mL, which is much lower than oral and intramuscular concentrations. Oral administration of a comparable dose of flunixin meglumine results in average concentrations ranging from 3,340 to 7,200 ng/mL. Intramuscular flunixin meglumine reaches average concentrations of 1,799-3,269 ng/mL.
- Transdermal absorption into the horse's bloodstream was slow, an average of 8.76 hours. Oral flunixin meglumine requires less than an hour to be absorbed.
- Elimination (clearance) of transdermal flunixin meglumine was also much slower than other routes of administration. It took 22 hours for half of the drug to be eliminated from the bloodstream (called the half-life) when the transdermal formulation was used. In contrast, the intravenous half-life is 3.38-9.68 hours.
- The data also showed that transdermal flunixin meglumine has unique pharmacokinetics called “flip-flop kinetics” in which the rate of absorption is actually slower than the rate of elimination.
“Based on this data, it is not surprising that flunixin meglumine and a metabolite were still detectable in urine 96 hours after application. This means that the withdrawal time for transdermal flunixin meglumine would be longer than for any other route of administration,” said Huntington.
He added, “Even though the blood concentrations of flunixin meglumine were lower compared to those achieved by other routes, the slow, variable absorption and 'flip- flop kinetics' indicate the medicine applied transdermally persists in the body longer than if given by other routes of administration. More excretion studies in exercising horses are needed before safe withholding periods before competition can be established.”
Despite the low circulating drug concentrations, transdermal flunixin meglumine still elicited an anti-inflammatory effect for up to 72 hours after application.
In terms of safety, Huntington warned, “Considering that transdermal flunixin meglumine is indeed absorbed systemically, this means that horses are at risk of the common side effects associated with NSAIDs administered by other routes: gastric ulceration, dorsal colitis, and disruption of the intestinal microbiome.”
Horses treated with any type of NSAID by any route of administration, including transdermal, would therefore benefit from a digestive tract supplement containing antacids, stomach-coating agents, and a hindgut buffer.
“These supplements reduce the risk of damage to the gut lining or change in the microbiota resulting from NSAID use,” Huntington advised.
*Knych, H.K., R.M. Arthur, S.R. Gretler, D.S. McKemie, S. Goldin, and P.H. Kass. 2021. Pharmacokinetics of transdermal flunixin meglumine and effects on biomarkers of inflammation in horses. Journal of Veterinary Pharmacology and Therapeutics:12993.
Reprinted courtesy of Kentucky Equine Research. Visit ker.com for the latest in equine nutrition and management, and subscribe to Equinews to receive these articles directly.
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