EVIDENCE FOR A PASSIVE DIFFUSION MECHANISM FOR SPARFLOXACIN UPTAKE ATTHE BRUSH-BORDER MEMBRANE OF THE HUMAN INTESTINAL CELL-LINE CACO-2

The oral uptake of the new fluoroquinolone sparfloxacin was evaluated in the human epithelial cell line Caco-2 that possesses intestinal ent erocyte-like properties when cultured in vitro. The uptake of [C-14]-s parfloxacin across the apical membrane of Caco-2 cell monolayers was r apid and similar at 25 and 37 degrees C. The initial rate of sparfloxa cin uptake was not saturable in the 1-200 mu M range and was unaffecte d by metabolic inhibitors (depletion of ATP store or ouabain), indicat ing that uptake was energy-independent. The absence of competition wit h other fluoroquinolones or aminocephalosporins showed that the absorp tion of sparfloxacin did not involved the H+-coupled dipeptide transpo rt system, Our findings suggest that the apical uptake of sparfloxacin by Caco-2 cells mainly involves diffusion, a finding that is in agree ment with the high lipophilicity of sparfloxacin. The intracellular-to -extracellular concentration ratio of similar to 14 after 60 min of in cubation suggests the existence of important binding of sparfloxacin t o cell components.