Active uptake of ulifloxacin from plasma to lung that controls its concentration in epithelial lining fluid
Abstract
Ulifloxacin is a new quinolone antibiotic and it is effective against pneumonia. We previously showed that it is highly distributed into the epithelial lining fluid (ELF) in rats, which might be resulting from certain active transport. The transport system has not been, however, clarified yet. In this study, we attempted to characterize the distribution mechanism of ulifloxacin into the rat ELF. We also aimed to elucidate the feature of ulifloxacin uptake in rat lung and human lung adenocarcinoma cells (Calu-3). In infusion studies, ulifloxacin concentrations in the ELF and lung were higher than that in the plasma, and decreased by co-administration of sparfloxacin or azithromycin to the level of plasma concentration. Integration plot analysis showed that active uptake of ulifloxacin from the plasma to lung was also inhibited by sparfloxacin and azithromycin. In in vitro studies, time and temperature-dependent uptake into Calu-3 was observed, and this uptake was inhibited by sparfloxacin and azithromycin as observed in the rat lung. Additionally sparfloxacin inhibited the active uptake of ulifloxacin into Calu-3 more strongly than levofloxacin as observed in the rat lung. These results suggest that active uptake of ulifloxacin from the plasma to lung controls the distribution of ulifloxacin from the plasma to ELF, and that the uptake of ulifloxacin into Calu-3 has partly similar characteristics to its uptake into the rat lung. We believe our study will contribute to much…
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