Pharmacokinetic Parameters and Estimated Milk Withdrawal Intervals for Domestic Goats (Capra Aegagrus Hircus) After Administration of Single and Multiple Intravenous and Subcutaneous Doses of Flunixin Meglumine

Abstract

Introduction:The study objectives were to estimate plasma flunixin (FLU) pharmacokinetic parameters and milk depletion profiles for FLU and its metabolite (5-hydroxy flunixin; 5-OH) after subcutaneous (SC) and intravenous (IV) administration of single and multiple flunixin meglumine (FM) doses to non-lactating (nulliparous and pregnant does) and lactating dairy goats. Analytical methods (ELISA and UPLC-MS/MS) for quantifying plasma FLU concentrations were compared. The final objective was to use regulatory (FDA and EMA) methods to estimate milk withdrawal intervals following extra-label drug use in goats.Methods: FM was administered IV and SC to commercial dairy goats at 1.1 mg/kg for single and multiple doses. Plasma and milk samples were analyzed for FLU and 5-OH via UPLC-MS/MS. Plasma samples were also analyzed for FLU concentrations via ELISA. Using statistical approaches recommended by regulatory agencies, milk withdrawal intervals were estimated following FM extra-label use.Results: Following IV administration of a single FM dose, clearances were 127, 199, and 365 ml/kg/h for non-lactating (NL) pregnant does, NL nulliparous does, and lactating dairy does, respectively. Following multiple SC doses, clearance/F was 199 ml/kg/h for lactating does. After IV administration of a single FM dose, terminal elimination half-lives were 4.08, 2.87, and 3.77 h for NL pregnant does, NL nulliparous does, and lactating dairy does, respectively. After multiple SC doses, the terminal elimination half-life was 3.03 h for lactating dairy does. No significant differences were noted for samples analyzed Smith et al.Dairy Goat Flunixin Meglumine Pharmacokinetics by UPLC-MS/MS or ELISA. Milk withdrawal intervals ranged from 36 to 60 h depending on the regulatory statistical method and dosage regimen.Conclusions: Subcutaneous administration of FM to goats results in similar plasma pharmacokinetic parameters as IV administration. ELISA analysis is an alternative method to UPLC-MS/MS for quantifying FLU concentrations in caprine plasma samples. Following FM extra-label administration to dairy goats, clinicians could consider 36-60 h milk withdrawal intervals.

Pharmacokinetics of Pantoprazole and Pantoprazole Sulfone in Goats After Intravenous Administration: A Preliminary Report

“…First calculated for each individual goat, and then combined for a mean value. With the goat cardiac output calculated as previously reported ( 20 , 21 ) as follows:…”

The pharmacokinetics of transdermal flunixin in lactating dairy goats

“…This data also suggests that the transdermal flunixin elimination in dairy goats in our study is faster than that in meat goats, which could be due to the increased metabolism and energy it takes to produce milk in lactating animals. Higher flunixin plasma clearance after SC and IV administrations in lactating goats was reported when compared with nonlactating goats (Smith et al, 2020). The mean plasma Cmax in dairy goats from this study was 0.13 µg/mL as compared with 0.134 µg/mL in meat goats (Reppert et al, 2019) and 1.17 µg/mL in .…”

“…To use the drug safely in lactating goats, it is critical to establish an appropriate milk WDI. The use of flunixin as an anti-inflammatory drug in goats and its pharmacokinetic parameters has been investigated for different routes of administration; including oral, intramuscular (IM), and intravenous (IV) (Königsson et al, 2003), subcutaneous (SC) in dairy goats (Smith et al, 2020), and transdermal in meat goats (Reppert et al, 2019). In a model of induced lameness in cattle, transdermal flunixin was able to provide some degree of analgesia (Kleinhenz et al, 2019).…”

“…This WDI calculation can change if different doses are used, a more sensitive assay is used (e.g., LOQ <0.001 µg/mL), or physiological status of animals changes. Using a different route of flunixin administration, formulation, and methodology, Smith et al (2020) reported a milk WDI estimate of 36 to 60 h in dairy cattle. It is important to remember that transdermal flunixin is not approved for use in dairy goats according to the FDA.…”

Pharmacokinetics of tulathromycin in pregnant ewes (Ovis aries) challenged with Campylobacter jejuni

“…In this study, ewes were pretreated with flunixin meglumine, which is a non-steroidal antiinflammatory used in the treatment of inflammatory conditions, including endotoxemia [30]. Previous unpublished studies in our laboratory have demonstrated that flunixin meglumine pretreatment diminishes the number of ewes that succumb to endotoxemia within the first 24 hours following IV administration of campylobacter.…”