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

Abstract

Funding information Iowa State University's College of Veterinary MedicineCeftiofur (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.

Ceftiofur formulation differentially affects the intestinal drug concentration, resistance of fecal Escherichia coli, and the microbiome of steers

“…The calves received 2 mg/kg of flunixin meglumine intravenously prior to surgery and 24 hours after surgery according to the IACUC protocol. There is no evidence of any impact on ceftiofur pharmacokinetics due to flunixin administration [20].…”

Impact of disease in dairy cows on ceftiofur pharmacokinetics, withdrawal times and emergence of antimicrobial resistance

“…In their work, they reported higher ISF CEF C max , a more rapid T max , but nearly identical AUC compared to the current work in a study utilizing healthy six-month old Holstein steers administered CEF sodium at 2.2 mg/kg. These C max and T max values were similar to the previous work, where ISF CEF concentration following CEF hydrochloride administration was determined (Gorden et al, 2017). Again, differences in kinetics of absorption likely account for these differences.…”

“…Maximum CEF concentrations in ISF were lower and time to reach maximum concentration was longer in the current trial compared to previous work (Gorden et al, 2017). In addition, CEF was detected in ISF for approximately 120 hours in the current study compared to 60 hours in the previous work.…”

“…Bound plasma drug concentration of CEF was determined on each cow on the T24, T96, and T192 hours plasma samples using a microcentrifugation system (Centrifree Ultrafiltration Device, EMD Millipore Corp., Billerica, MA) to collect plasma ultrafiltrate (UF), as previously described (Gorden et al, 2017). Following collection of plasma UF, samples were immediately frozen at -70 °C until analyzed for drug concentration.…”

A study to assess the correlation between plasma, oral fluid and urine concentrations of flunixin meglumine with the tissue residue depletion profile in finishing-age swine

“…It is labeled for use in the United States for beef cattle, dairy cattle, horses and swine [2,3]. It has been utilized with pharmacokinetic parameters assessed in numerous species [4][5][6][7][8][9][10][11][12][13][14][15][16]. Pharmacokinetic properties of FM have been described in smaller non-breeding aged swine with weights ranging from 20 kg to 40 kg [3,17,18], mature swine (152-168 kg) [19], and sows (187-259 kg) [20], but scant research findings exist on finishing-age swine (90-130 kg).…”