Transport of gatifloxacin involves Na+/Ca2+ exchange and excludes P-glycoprotein and multidrug resistance associated-proteins in primary cultured rat brain endothelial cells

The characteristics of gatifloxacin transport across blood brain barrier were investigated using primary cultured rat brain microvessel endothelial cells (rBMECs) as an in vitro model. Gatifloxacin uptake by rBMECs was time-, temperature- and energy-dependent. Gatifloxacin uptake by rBMECs was not influenced by P-glycoprotein (P-GP) inhibitor cyclosporine A or multidrug resistance associated-proteins (MRPs) inhibitor probenecid. However, verapamil inhibited the uptake in a concentration-dependent manner. Transendothelial transport study showed that transport of gatifloxacin across rBMEC monolayer was bidirectional, verapamil concentration-dependently inhibited transport from the apical to basolateral side, but did not significantly affect transport from basolateral to apical side. Gatifloxacin uptake was decreased in Ca2+-deprived medium but increased in Mg2+-deprived medium significantly. Furthermore, organic Ca2+ channel blockers nifedipine and diltiazem had no effect on gatifloxacin uptake, but inorganic Ca2+ channel blockers Ni2+ and Mg2+ inhibited the gatifloxacin uptake. The present study suggests that gatifloxacin transport across rBMECs involves a Na+/Ca2+ exchange mechanism and extracellular Ca2+ but not P-GP and MRPs.