Evidence for a passive diffusion mechanism for sparfloxacin uptake at the 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 enterocyte-like properties when cultured in vitro. The uptake of [14C]-sparfloxacin across the apical membrane of Caco-2 cell monolayers was rapid and similar at 25 and 37 degrees C. The initial rate of sparfloxacin uptake was not saturable in the 1-200 microM range and was unaffected by metabolic inhibitors (depletion of ATP store or ouabain), indicating that uptake was energy-independent. The absence of competition with other fluoroquinolones or aminocephalosporins showed that the absorption of sparfloxacin did not involved the H+-coupled dipeptide transport system. Our findings suggest that the apical uptake of sparfloxacin by Caco-2 cells mainly involves diffusion, a finding that is in agreement with the high lipophilicity of sparfloxacin. The intracellular-to-extracellular concentration ratio of approximately 14 after 60 min of incubation suggests the existence of important binding of sparfloxacin to cell components.