Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in alpacas.

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