Transport of gemifloxacin, a 4th generation quinolone antibiotic, in the Caco-2 and engineered MDCKII cells, and potential involvement of efflux transporters in the intestinal absorption of the drug.

1. The oral (po) bioavailability of gemifloxacin mesylate in rats and its possible association with efflux transporters was investigated. 2. The apparent permeabilities (P-app) of gemifloxacin across the Caco-2 cell monolayer were 1.20 +/- 0.09 x 10(-5) cm/s for apical to basal (absorptive) transport, and 2.13 +/- 0.6 x 10(-5) cm/s for basal to apical (secretory) transport for a 5-500 mu M concentration range, suggesting the involvement of a carrier-mediated efflux in the secretory transport. 3. The secretory transport in Caco-2 cells was significantly decreased by MRP2 (MK571) and BCRP (Ko143) inhibitors. 4. The secretory transport was distinct in MDCKII/P-gp, MDCKII/MRP2 and MDCKII/BCRP cells, and the affinity was highest for MRP2, followed by BCRP and P-gp. The efflux was significantly decreased by verapamil and Ko143, but not significantly by MK571. 5. The comparative po bioavailability in rats was increased by the preadministration of Ko143 (four-fold), MK571 (two-fold) and verapamil (two-fold). 6. Efflux transporters appeared to significantly limit the bioavailability of gemifloxacin in rats, suggesting their possible contribution to the low bioavailability of the drug in the human (70%).