BLOOD-BRAIN-BARRIER TRANSPORT RATE OF QUINOLONE ANTIBACTERIALS EVALUATED IN CEREBROVASCULAR ENDOTHELIAL-CELL CULTURES

The permeability of the blood-brain barrier (BBB) to ten quinolone ant ibacterials (gyrase inhibitors) was assessed in an in vitro model cons isting of primary cultures of bovine cerebrovascular endothelial cells . The transport kinetics across the cell monolayer was studied over a period of 90 min. The quinolone concentrations were determined by HPLC . The endothelial permeability P(e) expressing the transport rate diff ered considerably among individual quinolones, ranging from 0.54- 10(- 3) (enoxacin) to 0.58.10(-3) (A 60616) cm/min. P(e) was found to depen d on the octanol/buffer partition coefficient (log P) at pH 7.4 as a m easure for the lipophilicity of the compounds at physiological pH. The quantitative relationship between P(e) and log P allows a reliable pr ediction of the BBB permeability to new quinolone derivatives facilita ting the design of quinolones with increased CNS availability. There w as neither evidence of the presence of saturable transport mechanisms nor significant metabolism of quinolones at the BBB. The results sugge st that quinolones are transported across the BBB by passive diffusion .