title: Evidence for a passive diffusion mechanism for sparfloxacin uptake at the brush-border membrane of the human intestinal cell-line 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 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.
authors.affiliation: INRA, Laboratoire de Nutrition Humaine et de Physiologie Intestinale, Institut National Agronomique Paris-Grignon, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Cormet
authors.forename: J F
authors.initials: JF
authors.lastname: Huneau
authors.forename: M
authors.initials: M
authors.lastname: Bouras
authors.forename: C
authors.initials: C
authors.lastname: Carbon
authors.forename: E
authors.initials: E
authors.lastname: Rubinstein
authors.forename: D
authors.initials: D
authors.lastname: Tomé
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D004058:Diffusion; D024841:Fluoroquinolones; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D008871:Microvilli / Q000378:metabolism; D015363:Quinolones / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C061363:sparfloxacin