Comparison of milk and plasma pharmacokinetics of meloxicam in postpartum versus mid-lactation Holstein cows.

The objective of this study reported here was determine whether differences occurred in meloxicam pharmacokinetics between postpartum cows and mid-lactation cows. Preliminary data from a separate study (P. J. Gorden, unpublished data) in postpartum cows demonstrated elevated plasma and milk concentration profiles compared to previously published data (Malreddy, Coetzee, KuKanich, & Gehring, ). Two different groups were enrolled, each with 10 cows. The treatment group (TRT) was postpartum cows treated with meloxicam, and the positive control (PC) group was cows in mid-lactation treated with meloxicam. Plasma and milk meloxicam concentrations between the TRT and PC group were compared. Significant differences in meloxicam concentration in plasma were determined at all time points from 8 hr to 120 hr post-treatment. In milk, there was a treatment (p = .003), time (p < .001), and treatment by time interaction (p < .001). Significant differences in milk meloxicam concentration were determined at all time points from 8 hr to 96 hr post-treatment, except for the 16-hr time point. The time needed for meloxicam to no longer be detected in milk of the TRT group was longer compared to the PC group, indicating that a longer milk withdrawal is needed. These data suggest higher bioavailability as the underlying mechanism. Further research is needed to determine the mechanisms underlying differences this outcome.

Comparative plasma and interstitial fluid pharmacokinetics of flunixin meglumine and ceftiofur hydrochloride following individual and co-administration in dairy cows.

Ceftiofur (CEF) and flunixin meglumine (FLU) are two drugs approved for use in beef and dairy cattle that are frequently used in combination for many diseases. These two drugs are the most commonly used drugs in dairy cattle in their respective drug classes. Two research groups have recently published manuscripts demonstrating altered pharmacokinetics of FLU and CEF in cows affected with naturally occurring mastitis. The objective of this study was to determine whether pharmacokinetics of flunixin meglumine administered intravenously or intramuscularly administered ceftiofur hydrochloride would be altered when co-administered versus individual administration to healthy dairy cattle. Ten cows were utilized in a three-period, three-treatment crossover design, with all cows receiving each treatment one time with a 10-day washout period between treatments. Following treatment, plasma and interstitial fluid samples were collected and stored for later analysis. Additionally, plasma ultrafiltrate was collected using microcentrifugation to determine plasma protein binding of each drug. Drug concentrations in plasma, plasma ultrafiltrate, and interstitial fluid were determined using high-pressure liquid chromatography coupled with mass spectrometry. The results of this trial indicate that drug interactions between FLU and CEF do not occur when the two drugs are administered simultaneously in healthy cattle. Further work is needed to determine whether this relationship is maintained in the presence of severe disease.