Pharmacokinetics of Flunixin after Intravenous Administration in Healthy and Endotoxaemic Rabbits

The pharmacokinetics of flunixin were determined after intravenous bolus injection at a single dose (2.2 mg/kg) in healthy rabbits and diseased rabbits with Escherichia coli lipopolysaccharide-induced septic shock. Six adult New Zealand White rabbits were used. Concentrations of drug in plasma were determined by HPLC. Pharmacokinetics were best described by a two-compartment open model. In healthy rabbits, there was a high plasma clearance (0.62 L/(h kg)), and a relatively short elimination half-life (1.19 h). In endotoxaemic rabbits, total plasma clearance (0.43 L/(h kg)) was significantly lower (p<0.05), and elimination half-life (1.90 h) and AUC₀-∞ (5.29 (μg h)/ml) were significantly higher (p<0.05) than in healthy animals. The changes of pharmacokinetics of flunixin in rabbits with septic shock could be of clinical significance, and may require monitoring of plasma flunixin levels in endotoxaemic status.