COMPARATIVE UPTAKE OF SPARFLOXACIN AND CIPROFLOXACIN INTO HUMAN THP-1MONOCYTIC CELLS - EVIDENCE FOR AN ORGANIC ANION TRANSPORT

The uptake of sparfloxacin (CAS 11542-93-9) by human monocytes was stu died by comparison with ciprofloxacin (GAS 86393-32-0). The human mono cytic THP 1 cells were incubated with the antibiotics for 2 h. Entry o f antimicrobials into the cells was determined by means of a velocity gradient centrifugation technique and HPLC assay. Antibiotic uptake wa s expressed as the ratio of the intracellular to the extracellular dru g concentration (IC/EC). Quinolones enter readily in monocytic cells b ut sparfloxacin is taken up more rapidly than ciprofloxacin. At steady -state the IC/EC ratio of sparfloxacin (9.07) is higher than IC/EC of ciprofloxacin (4.29). Characterization of quinolone uptake suggests th at these drugs penetrate throughout the THP 1 membrane by passive diff usion. However, the results of the present study indicate that additio nal mechanisms may contribute to intracellular accumulation of ciprofl oxacin and sparfloxacin. Gemfibrozil, an inhibitor of organic anion tr ansport, increases the accumulation of ciprofloxacin but does not modi fy IC/EC of sparfloxacin. It can be concluded that human monocyte-like cells have functinal organic anion transporters and that this way of secretion is quinolone selective.