Correlation between quinolone uptakes by BCECs in vitro and brain-to-plasma concentration ratios in rats.

Transport of 11 quinolones at the blood-brain barrier (BBB) was studied in vitro by using primarily cultured rat brain capillary endothelial cells (BCECs) and in vivo brain-to-plasma concentration ratios. In vitro, when cells reached confluence, a time course of quinolone uptake was recorded by incubation with a medium contraining quinolones 20 microg/ml at 37 degrees C. A simple two-compartment model was used for fitting the uptake time course and corresponding uptake parameters were estimated. In vivo rats were anesthetized, after in 10 mg/kg of quinoloes followed by infusion of 4 mg/kg/h for 2 hours, the drug concentrations in plasma and brain were measure and brain-to-plasma concentration ratios were calculated. Result showed that sparfloxacin and prulifloxacin have higher uptakes by BCECs and brain-to-plasma concentration ratios, compared with other quinolones, which indicated that the two drugs more easily penetrate into BBB. A good correlation between uptakes by BCECs and brain-to-plasma concentration ratios was found. These results demonstrated uptakes by BCECs in vitro might give prediction of brain-to-plasma ratio for quinolones.