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

Emily J Reppert, Michael D Kleinhenz, Shawnee R Montgomery, Heather N Bornheim, Geraldine Magnin, Pritam K Sidhu, Yuntao Zhang, Hyun Joo, Johann F Coetzee
Journal of Veterinary Pharmacology and Therapeutics 2019 February 25
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.


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