Is the uptake of pefloxacin in human blood monocytes a simple diffusion process?

Effective therapy of infections caused by facultative intracellular micro-organisms, which persist after ingestion by mononuclear phagocytic cells, requires antibiotics which inactivate these intraphagocytic bacteria. A previous study demonstrated that intracellular concentrations of normethylpefloxacin, Ci, were the result of simple diffusion and an active efflux involving organic anion transporters. In our work, we studied pefloxacin transport in human monocytes. A kinetic approach was followed to establish the processes involved. Extracellular concentrations, Ce, corresponding to in-vivo pharmacological levels of the drug were used. Uptake of the antibiotic was assessed principally by HPLC. Pefloxacin was accumulated by the cells (Ci/Ce = 3). The uptake was rapid, non saturable, reversible and temperature dependent. At 4 degrees C, the Ci/Ce was equal to 1. At high temperatures, an active and initial process appeared that was not visible at lower temperatures and disappeared in presence of energetic metabolism inhibitor: At 42 degrees C, NaCN and 2.4 DNP (1 mM) reduced the initial transport but they had no significant effect on the subsequent curve.