Transport characteristics of grepafloxacin and levofloxacin in the human intestinal cell line Caco-2

Transport characteristics of grepafloxacin and levofloxacin across the apic al membrane of Caco-2 cells were examined. Both grepafloxacin and levofloxa cin uptakes increased rapidly, and were temperature-dependent. Grepafloxaci n and levofloxacin uptakes showed concentration-dependent saturation with M ichaelis constants of 3.9 and 9.3 nM, respectively. Uptake of grepafloxacin and levofloxacin increased in Cl--free and ATP depleted conditions, sugges ting the involvement of an efflux transport system different from the uptak e mechanism. However, cyclosporin A, a typical inhibitor of P-glycoprotein, did not affect the uptake of these drugs. Unlabeled grepafloxacin, unlabel ed levofloxacin and quinidine inhibited the uptake of grepafloxacin and lev ofloxacin under Cl--free conditions. Tetraethylammonium, cimetidine, p-amin ohippurate, probenecid, amino acids, beta -lactam antibiotic or monocarboxy lates did not inhibit the uptake of grepafloxacin and levofloxacin under th e same conditions. In conclusion, our results suggested that grepafloxacin and levofloxacin uptakes were mediated by a specific transport system disti nct from those for organic cations and anions, amino acids, dipeptides and monocarboxylates. (C) 2001 Elsevier Science B.V. All rights reserved.