Short communication: Determination of the milk pharmacokinetics and depletion of milk residues of flunixin following transdermal administration to lactating Holstein cows

摘要

Flunixin is a nonsteroidal anti-inflammatory drugand the most commonly prescribed analgesic in cattlein the United States. Recently, the US Food and DrugAdministration (FDA) approved a transdermal formulationof flunixin for control of pyrexia associated withbovine respiratory disease and the control of pain associatedwith foot rot. The transdermal formulation isnot currently approved for use in lactating dairy cattlein the United States, but extra-label use in dairy cattleis permissible under US regulations. The objectives ofthis study were to determine the pharmacokinetics inmilk of dairy cows treated with transdermal flunixinand determine an appropriate withdrawal time formilk. Ten lactating Holstein cows were enrolled intothe study in mid lactation. Following treatment, cowswere milked 3 times per day through 144 h. Milksamples were collected for drug analysis using ultrahigh-pressure liquid chromatography coupled with atriple quadrupole mass spectrometer. The geometricmean maximum concentration for flunixin in milkwas 0.010 μg/mL and was 0.061 μg/mL for the activemetabolite, 5-hydroxyflunixin. The geometric meanterminal half-life was 20.71 h for flunixin and 22.62 hfor 5-hydroxyflunixin. Calculations to approximate awithdrawal time in milk following transdermal flunixinadministration were accomplished using a statisticaltolerance limit procedure. This analysis indicated thatit would be prudent to observe a withdrawal period of96 h following the last treatment. This is more thantwice as long as the labeled withdrawal period of 36 hfollowing use of the injectable formulation. The withdrawalperiod suggested by this work should be appliedcarefully, as this study was not conducted underthe full quality control practices required by the USFDA for a full drug approval study. Caution should betaken when applying this withdrawal time to diseasedanimals, animals that are milked with different milkingfrequencies, and those in different stages of productionas these have all been shown to affect drug depletionfrom milk.