Pharmacokinetics of Flunixin after Intravenous Administration in Healthy and Endotoxaemic Rabbits

Abstract

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 AUC(0-infinity) (5.29 (microg 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.

Normal values of haematological and some biochemical parameters in serum and urine of New Zealand White rabbits

“…Total protein, albumin, glucose, creatinine, BUN, Ca, P, Na, K and Cl levels determined in this study and presented in Table 2 were within the range of reference values reported for rabbits in previous studies (Yu et al, 1979;Hewitt et al, 1989;Lepitzki and Woolf, 1991;Yazar et al, 2004;Silva et al, 2005;Elmas et al, 2006;Melillo, 2007). No statistically significant difference for any parameters, except serum K concentration, was determined in this study between male and female rabbits.…”

“…Serum GGT activity was higher than was found in other studies (Yu et al, 1979;Hewitt et al, 1989;Tavares et al, 2004;Yazar et al, 2004;Elmas et al, 2006;Melillo, 2007). AST activity was near to the levels reported in some previous studies (Yu et al, 1979;Tavares et al, 2004) and lower than the levels observed in some others (Lepitzki and Woolf, 1991;Silva et al, 2005;Elmas et al, 2006;Melillo, 2007).…”

Effects of Acute Hepatic and Renal Failure on Pharmacokinetics of Flunixin Meglumine in Rats

“…In the present study, CCl 4 treatment induced apparent liver dysfunction without renal damage, and glycerol treatment induced marked renal dysfunction with little liver injury. These results are mostly consistent with the previous studies [5,10]. Therefore, our results confirm that CCl4 and glycerol treatment induce selective hepatic and renal dysfunction.…”

“…Flunixin acts through the inhibition of cyclooxygenase, which synthesizes prostaglandins from arachidonic acid [12]. Flunixin has been used for the control of postoperative pain and the treatment of respiratory diseases, mastitis, osteoarthritis, and endotoxemia in a variety of animals [2,6,11]. Pharmacokinetic profiles of flunixin are characterized by good bioavailability, short half-life and a high protein binding property.…”

Influences of flunixin and tenoxicam on the pharmacokinetics of florfenicol in lipopolysaccharide-induced endotoxemia

“…However, this value slightly increased in coadministration of FF-FM-LPS and FF-TN-LPS when compared with FF-LPS in animal groups. As a result, increasing the AUC (0)(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and lengthening the t 1/2λz may be related to decreasing the Cl T of FF in coadministered groups in endotoxemic rabbits. In our study, the V ss of FF was large (from 1.85 ± 0.12 to 2.21 ± 0.06 L/kg).…”