Influence of Escherichia coli Endotoxin-Induced Endotoxaemia on the Pharmacokinetics of Enrofloxacin after Intravenous Administration in Rabbits

Authors


Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, Konya, Turkey

Summary

The main goal of present study was to determine the effects of an Escherichia coli endotoxin-induced endotoxaemic status on disposition of enrofloxacin after a single intravenous dose (5 mg/kg) in rabbits. Septic shock was induced by the i.v. bolus administration at a single dose of E. coli lipopolysaccharide. Six adult New Zealand White rabbits were used. Concentrations of drug in plasma were determined by HPLC. The plasma pharmacokinetic values for enrofloxacin were best represented using a two-compartment open model. Total plasma clearance (ClT) decreased from 2.11 (l/h/kg) in healthy animals to 1.50 (l/h/kg) in rabbits with septic shock, which is related to an increase in the AUC0→∞. In endotoxaemic rabbits, volume of distribution at steady state (Vdss = 3.61 l/kg) was significantly lower (P < 0.05) than in healthy animals (Vdss = 4.97 l/kg). However, the elimination half-life of enrofloxacin was not affected by lipopolysaccharide administration.

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