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.