Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in alpacas

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, 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 E 2 concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE 2 concentrations decreased after IV flunixin meglumine administration but there was minimal change after TD application. Mean t 1/2 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 C max, T max and t 1/2 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 (IC 80 ) of PGE 2 by flunixin meglumine was 0.23 µg/ml (range, 0.01 to 1.38 µg/ml). Poor bioavailability and poor suppression of PGE 2 identified in this study indicate that TD flunixin meglumine administered at 3.3 mg/kg is not recommended for use in alpacas.