Transport characteristics of grepafloxacin and levofloxacin in the human intestinal cell line Caco-2.
Transport characteristics of grepafloxacin and levofloxacin across the apical membrane of Caco-2 cells were examined. Both grepafloxacin and levofloxacin uptakes increased rapidly, and were temperature-dependent. Grepafloxacin and levofloxacin uptakes showed concentration-dependent saturation with Michaelis constants of 3.9 and 9.3 mM, respectively. Uptake of grepafloxacin and levofloxacin increased in Cl(-)-free and ATP depleted conditions, suggesting the involvement of an efflux transport system different from the uptake mechanism. However, cyclosporin A, a typical inhibitor of P-glycoprotein, did not affect the uptake of these drugs. Unlabeled grepafloxacin, unlabeled levofloxacin and quinidine inhibited the uptake of grepafloxacin and levofloxacin under Cl(-)-free conditions. Tetraethylammonium, cimetidine, p-aminohippurate, probenecid, amino acids, beta-lactam antibiotic or monocarboxylates did not inhibit the uptake of grepafloxacin and levofloxacin under the same conditions. In conclusion, our results suggested that grepafloxacin and levofloxacin uptakes were mediated by a specific transport system distinct from those for organic cations and anions, amino acids, dipeptides and monocarboxylates.
Yamaguchi
H
H
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Yano
I
I
Saito
H
H
Inui
K
K
D000255:Adenosine Triphosphate / Q000737:chemistry; D000890:Anti-Infective Agents / Q000378:metabolism*; D001692:Biological Transport; D018938:Caco-2 Cells; D002250:Carbon Radioisotopes; D002712:Chlorides / Q000737:chemistry; D016572:Cyclosporine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D064704:Levofloxacin; D015242:Ofloxacin / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism*
D000890:Anti-Infective Agents; D002250:Carbon Radioisotopes; D002712:Chlorides; D024841:Fluoroquinolones; D010879:Piperazines; D064704:Levofloxacin; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D015242:Ofloxacin; C075375:grepafloxacin