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

摘要

The purpose of this study was to investigate the influences of flunixin (FM) and tenoxicam (TN) on the pharmacokinetics of florfenicol (FF) after coadministration in lipopolysaccharide (LPS)-induced endotoxemic rabbits. Fifteen male rabbits were used in this study. FF (20 mg/kg), FM (2 mg/kg), and TN (1 mg/kg) were coadministered via intravenous injection to the animals. The concentrations of FF were determined by high-performance liquid chromatography with diode-array detection from 0.08 to 12 h in plasma. The plasma concentration-time profile of FF was described using a noncompartmental open model. In this study, terminal half-life, area under the curve, mean residence time, and volume of distribution at steady state were significantly increased, whereas total body clearance was decreased in coadministered groups. In conclusion, FM and TN have effects on the pharmacokinetics of FF in coadministered endotoxemic rabbits. When FF is coadministered with FM and TN, it can be given at a dose of 20 mg/kg b.w. every 8 h for treatment of infections caused by susceptible pathogens with a minimum inhibitory concentration (MIC) of <= 2 mu g/mL or 12 h for treatment of infections caused by susceptible pathogens with MIC of <= 1 mu g/mL in critically ill rabbits. Further studies are necessary to determine variations in dosage regimens.