Evidence for a Passive Diffusion Mechanism for Sparfloxacin Uptake at the Brush-Border Membrane of the Human Intestinal Cell-linec Caco-2

Abstract

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°C. The initial rate of sparfloxacin uptake was not saturable in the 1–200 µM 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 ∼14 after 60min of incubation suggests the existence of important binding of sparfloxacin to cell components.