Comparative study of the disposition of levofloxacin, netilmicin and cefepime in the isolated rat lung

Abstract

An experimental model of artificially perfused and mechanically ventilated lung has been applied to compare the kinetic behaviour of levofloxacin, cefepime and netilmicin in this body tissue. The study has been performed to explore the usefulness of the isolated lung technique in the pharmacokinetic field, particularly to study the disposition of antibiotics in pulmonary tissue. The lung was perfused with Krebs-Henseleit medium containing 3% bovine albumin at a flow rate of 5 mL min−1. It was ventilated at 60 respirations/min with a 2-mL tidal volume of air previously humidified and warmed to 37°C. The concentrations of the above antibiotics were determined by HPLC techniques and the outflow curves were analysed by stochastic, as well as by model-dependent, methods. The results show pharmacokinetic differences among these antibiotics, which are in accordance with previously reported data, levofloxacin being the drug with the highest distribution coefficient in this tissue (1.25 ± 0.14 vs 0.39 ± 0.07 and 0.41 ± 0.06 mL g−1 for netilmicin and cefepime, respectively). Accordingly, the isolated lung of the rat, under the experimental conditions used here, constitutes an alternative model to be incorporated to pharmacokinetic studies with a great potential use for those drugs that show a pharmacological or toxicological action depending on the kinetic profile in the lung tissue.