Determination of flunixin residues in milk following transdermal administration

Lucas Pantaleon

Flunixin meglumine is a nonsteroidal anti-inflammatory drug (NSAID). In the US it is the most commonly prescribed analgesic for cattle. An injectable flunixin formulation has been available in the US market labeled for intravenous treatment of dairy cattle with fever associated with bovine respiratory disease and endotoxic mastitis, and the treatment of endotoxemia associated with coliform mastitis.

The US Food and Drug Administration (FDA) recently approved a transdermal formulation of flunixin for the treatment of fever associated with bovine respiratory disease and pain due to foot rot. To date, this formulation has not been approved for treatment in lactating dairy cattle. However extra-label use is permissible in dairy cattle under US regulations for indications that are not associated with the injectable formulation. In case of extra-label use the prescribing veterinarian is responsible for assuring that there is no residue in milk or meat post treatment.

Since there is no label claim for transdermal administration of flunixin, no data exists on the withholding length period in milk. The aim of the study discussed here (Gorden et al., 2019) was to assess the appropriate milk withdrawal time after transdermal flunixin administration in lactating dairy cows. In the US the depletion of flunixin from milk is assessed by measuring its metabolite 5-hydroxyflunixin (5-OH-FLU).

This study enrolled 10 Holstein cows in mid lactation, cows were milked 3 times daily. A composite milk sample was collected pretreatment (time 0). Treatment consisted of transdermal flunixin at a dose of 3.3 mg/kg every 24 hours twice. At each milking, a composite sample was collected during the 144 hours (6 days) of the study. At the laboratory milk concentration of flunixin and its metabolite were determined.

There was no residue of flunixin or 5-OH-FLU in milk at time 0 (before treatment). After topical flunixin administration, flunixin was present in all milk samples through 96 hours from the last treatment, and up to 120 hours in 3 cows. The flunixin metabolite was found in all treated cows up to 120 hours (5 days) after the last treatment.

In this preliminary analysis, calculations to approximate the withdrawal time in milk following transdermal flunixin administration concluded that a period of 96 hours should be observed after the last treatment. Based on the current study, transdermal administration of flunixin carriers a much longer withdraw period compared to the injectable formulation which is 36 hours after the last administration.

It is important to notice that this study was not conducted under the full quality control practices mandated by the US FDA for a full drug approval study. Furthermore, this study was performed in healthy cows, hence applying these results to ill cows should be done with caution.

Reference

Gorden, P. J., Kleinhenz, M. D., Warner, R., Sidhu, P. K., and Coetzee, J. F. (2019). Determination of the milk pharmacokinetics and depletion of milk residues of flunixin following transdermal administration to lactating Holstein cows. Journal of Dairy Science, 102(12), 11465-11469.

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