Kinetic analysis of the transport of the quinolone antibiotics across the blood-brain barrier and blood-CSF barrier

The modified distributed model was constructed to analyze the distribution of quinolone antibiotics (NQs) in the rat brain. Eight-fold variations among NQs examined were observed for both the brain-to-plasma unbound concentration ratio (Kp, f(brain)) and the cerebrospinal fluid-to-plasma unbound concentration ratio (Kp, f(CSF)). The influx rates of NQs at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (B-CSF-B) were found to be determinant for Kp, f(brain) and Kp, f(CSF), respectively. Moreover, both the influx rates of NQs were correlated well with the octanol-water partition coefficients. Interestingly, only little effect of efflux rate at the B-CSF-B on Kp, f(CSF) was demonstrated, while in vitro uptake studies using isolated choroid plexus revealed that NQs was pumped out from cerebrospinal fluid to the circulating blood by an active organic anion transport system. In conclusion, the differential BBB permeability is suggested to a determinant for the brain interstitial fluid concentration of NQs which is believed to be responsible for toxicological effect on the central nervous system.