Drug disposition study on a levofloxacin dry powder formulation using the isolated perfused lung in rats
Abstract
In this study, using an artificially perfused and mechanically ventilated lung as an experimental model, levofloxacin disposition after bolus and pulmonary delivery has been compared. This model was used to investigate the absorption of levofloxacin through the airway into the blood. Krebs-Ringer buffer medium containing bovine serum albumin was perfused into the lungs at a rate of 4 ml.min− 1. The lungs were ventilated with humidified air heated to 37 °C at 60 breaths per minute. Levofloxacin was administered into the perfusion circuit as a bolus injection and into inhalation air (dry powder). By using HPLC combined with UV detection, the concentration of levofloxacin (in efferent) was determined after lung perfusion. Levofloxacin transported from lung to blood and was detectable within an hour of the experiment, although due to rapid elimination it was no longer detectable 20 min after bolus administration. The normalized AUC0−inf. after administration of dry powder and solution were 34209.17 ± 6446.1 and 329371.02 ± 94627.7 ng.min.ml− 1.mg− 1, respectively. At the end of the experiment, higher levels of levofloxacin were detected in the lungs via pulmonary administration. This ex vivo model resulted in localized delivery of levofloxacin to the lung compartment and measurable transfer into the perfusate.
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