SECRETION OF SPARFLOXACIN FROM THE HUMAN INTESTINAL CACO-2 CELL-LINE IS ALTERED BY P-GLYCOPROTEIN INHIBITORS

The mechanism of intestinal secretion of the difluorinated quinolone s parfloxacin was investigated with the epithelial cell line Caco-2 and was compared to that of the P-glycoprotein (P-gp) substrate vinblastin e. The P-gp inhibitors verapamil and progesterone significantly increa sed the epithelial cell accumulation of both vinblastine and sparfloxa cin. This increase is likely to result from an inhibition of drug secr etion since both vinblastine uptake and sparfloxacin uptake are known to proceed through a passive transmembrane diffusion. The unidirection al Ruses across cell monlayers grown on permeable filters indicated th at a net secretion of sparfloxacin and vinblastine occurred across Cac o-2 cells. These secretions were significantly inhibited by the MDR-re versing agent verapamil. We conclude that the P-gp is likely to be inv olved in the intestinal elimination of the difluorinated quinolone spa rfloxacin.