Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in meat goats

Abstract

The aim of this study was to determine the pharmacokinetics and prostaglandin E2 (PGE2) synthesis inhibiting effects of intravenous (IV) and transdermal (TD) flunixin meglumine in eight adult female Boer goats. A dose of 2.2 mg/kg was administered intravenously (IV) and 3.3 mg/kg administered TD using a cross‐over design. Plasma flunixin concentrations were measured by LC‐MS/MS. Prostaglandin E2 concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE2 concentrations decreased after flunixin meglumine for both routes of administration. Mean λz‐HL after IV administration was 6.032 hr (range 4.735–9.244 hr) resulting from a mean Vz of 584.1 ml/kg (range, 357.1–1,092 ml/kg) and plasma clearance of 67.11 ml kg−1 hr−1 (range, 45.57–82.35 ml kg−1 hr−1). The mean Cmax, Tmax, and λz‐HL for flunixin following TD administration was 0.134 μg/ml (range, 0.050–0.188 μg/ml), 11.41 hr (range, 6.00–36.00 hr), and 43.12 hr (15.98–62.49 hr), respectively. The mean bioavailability for TD flunixin was calculated as 24.76%. The mean 80% inhibitory concentration (IC80) of PGE2 by flunixin meglumine was 0.28 μg/ml (range, 0.08–0.69 μg/ml) and was only achieved with IV formulation of flunixin in this study. The PK results support clinical studies to examine the efficacy of TD flunixin in goats. Determining the systemic effects of flunixin‐mediated PGE2 suppression in goats is also warranted.

Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in alpacas

“…Recent studies have demonstrated differences in pharmacokinetics of TD flunixin meglumine between cattle and goats (Kleinhenz et al, ; Reppert et al, ). The pharmacokinetic parameters of TD flunixin in alpacas varied from goats and cattle.…”

“…Prostaglandin E 2 inhibition has been used as a measure to determine efficacy of flunixin meglumine in several species (Kleinhenz et al, ; Königsson, Törneke, Engeland, Odensvik, & Kindahl, ; Reppert et al, ). In this study, PGE 2 inhibition was quantified for both IV and TD flunixin meglumine formulations.…”

“…The analysis was carried out using a Waters Xevo TQ‐S triple quadrupole mass spectrometer as described previously (Reppert et al, ). In brief, an Acquity UPLC HSS T3 column (1.8 μm, 2.1 × 50 mm) was held at 40°C with eluents composed of mobile phase A (0.1% formic acid in water) and mobile phase B (0.1% formic acid in acetonitrile).…”

“…Plasma PGE 2 concentrations were determined using methods adapted from Fraccaro et al () and Kleinhenz et al () (Reppert et al, ). Briefly, 1 ml of blood was collected from samples collected before drug administration and at 1, 2, 4, 12, 24 and 48 hr postdrug administration prior to centrifugation.…”

“…In Holstein calves, TD flunixin meglumine was rapidly absorbed and had a longer half‐life than IV administration of the drug (Kleinhenz et al, ). However, in goats, TD flunixin meglumine had prolonged absorption and lower bioavailability compared to cattle (Reppert et al, ).…”