Comparative uptake of grepafloxacin and ciprofloxacin by a human monocytic cell line, THP-1

The present study was designed to compare the uptake of grepafloxacin by a human monocytic cell line, THP-1, with that of ciprofloxacin. THP-1 cells were incubated with 20 μg/ml of either drug, and the entry of the drugs into the cells was determined using a velocity gradient centrifugation technique and HPLC assay. Antibiotic uptake by the cells was expressed as the ratio of the intracellular to the extracellular drug concentration (IC/EC). Grepafloxacin entered THP-1 cells readily within 5 min, and at steady-state (37°C; 60 min), the IC/EC ratio of grepafloxacin (11.9 ± 1.7; n = 13) was about 2.4-fold higher than that of ciprofloxacin (5.0 ± 1.3; n = 13). The ratios decreased at low incubation temperature (4°C), in paraformaldehyde-treated dead cells, and at low extracellular pH (pH 6.0), but were not influenced by high extracellular pH (pH, 9.0). Characterization of fluoroquinolone uptake suggests that these drugs penetrate the THP-1 membrane by passive diffusion, and also, in part, via an active transport system. We also examined the uptake of the two fluoroquinolones in phorbol 12 myristate 13-acetate (PMA)-stimulated adherent THP-1 cells (THP-1 macrophages). The IC/EC ratios for both fluoroquinolones in the THP-1 macrophages were significantly higher than those in the THP-1 monocytes. Further the uptake of three other fluoroquinolones, levofloxacin, tosufloxacin, and sparfloxacin, by THP-1 monocytes was examined in comparative studies. The IC/EC ratio of grepafloxacin was comparable to that of sparfloxacin and significantly higher than that of the other fluoroquinolones. Our results indicate that grepafloxacin exhibits better intracellular accumulation than ciprofloxacin and other fluoroquinolones in human monocytic and macrophage-like cells. Received: June 1, 2000 / Accepted: August 1, 2000