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Pharmacokinetics and Pharmacodynamics of Intravenous and Transdermal Flunixin Meglumine in Alpacas

Pharmacokinetics and Pharmacodynamics of Intravenous and Transdermal Flunixin Meglumine in Alpacas

Emily J Reppert, Michael D Kleinhenz, Shawnee R Montgomery, Jared Heiman, Amanda Sura, Heather N Bornheim, Geraldine Magnin, Pritam K Sidhu, Yuntao Zhang, Hyun Joo, Johann F Coetzee

J Vet Pharmacol Ther. 2019 Sep;42(5):572-579.

PMID: 31353535

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, Huacaya alpacas. A dose of 2.2 mg/kg administered 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 IV flunixin meglumine administration but there was minimal change after TD application. Mean t1/2 λz after IV administration was 4.531 hr (range 3.355 to 5.571 hr) resulting from a mean Vz of 570.6 ml/kg (range, 387.3 to 1,142 ml/kg) and plasma clearance of 87.26 ml kg-1 hr-1 (range, 55.45-179.3 ml kg-1 hr-1 ). The mean Cmax, Tmax and t1/2 λz for flunixin following TD administration were 106.4 ng/ml (range, 56.98 to 168.6 ng/ml), 13.57 hr (range, 6.000-34.00 hr) and 24.06 hr (18.63 to 39.5 hr), respectively. The mean bioavailability for TD flunixin was calculated as 25.05%. The mean 80% inhibitory concentration (IC80 ) of PGE2 by flunixin meglumine was 0.23 µg/ml (range, 0.01 to 1.38 µg/ml). Poor bioavailability and poor suppression of PGE2 identified in this study indicate that TD flunixin meglumine administered at 3.3 mg/kg is not recommended for use in alpacas.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP42461847-A	Flunixin meglumine		42461-84-7	Price
AP6284408-A	Meglumine		6284-40-8	Price

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