Abstract

For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been considered as the gold standard for estimating the antibacterial efficacy. In this study, the pharmacokinetics of florfenicol (FF) in porcine lung interstitial fluid was investigated after single intramuscular administration at two different doses (20 and 50mg/kg). Twelve pigs underwent thoracotomy under general anesthesia. Then, the CMA/30 probe was implanted into the lung and perfused at 1μL/min. The microdialysis (MD) samples were collected on a preset schedule and analyzed by high-performance liquid chromatography (HPLC). Noncompartmental pharmacokinetic analysis was performed. FF exhibited rapid distribution and slow elimination in porcine lung interstitial fluid. The main pharmacokinetic parameters at 20 and 50mg/kg were 4.88±0.54 and 10.36±2.52μg/mL for the maximum concentration (Cmax ), 3.25±0.32 and 3.50±0.27h for the time to Cmax (Tmax ), 9.47±6.84 and 7.75±3.23h for the half-life (t1/2 ), 0.10±0.06 and 0.10±0.04 1/h for the terminal elimination rate constant (λz ), 13.85±7.97 and 11.42±2.79h for the mean residence time (MRT), 37.77±8.13 and 71.15±16.99h·μg/mL for the area under the curve from time 0 to 18.25h (AUC0-18.25 ), and 51.18±20.11 and 88.78±27.58h·μg/mL for the area under the curve from time 0 to infinity (AUC0-∞ ), respectively.

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