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

Abstract

Abstract The aim of this study was to determine the pharmacokinetics and prostaglandin E 2 ( PGE 2 ) 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 E 2 concentrations were determined using a commercially available ELISA . Pharmacokinetic ( PK ) analysis was performed using noncompartmental methods. Plasma PGE 2 concentrations decreased after flunixin meglumine for both routes of administration. Mean λ z ‐ HL after IV administration was 6.032 hr (range 4.735–9.244 hr) resulting from a mean V z 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 C max , T max, and λ z ‐ 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 ( IC 80 ) of PGE 2 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 PGE 2 suppression in goats is also warranted.