Purpose. It is reported that the cerebrospinal fluid (CSF) to plasma unbound concentration ratio of fleroxacin at steady-state is approximately 0.5 in experimental animals. These results can be accounted for by assuming the presence of an active transport system for the efflux of this compound across the choroid plexus. In the present study, the transport system for fleroxacin was characterized in isolated rat choroid plexus. Methods. Choroid plexus was isolated from the lateral ventricles of rats. The accumulation of [14C] fleroxacin or [3H] benzylpenicillin by the choroid plexus was examined by the centrifugal filtration method. Results. The accumulation of [14C] fleroxacin by the rat isolated choroid plexus was significantly inhibited by metabolic inhibitors (rotenone, 30 μM and carbonyl cyanide p-trifluorometh oxyphenylhydrazone (FCCP), 100 μM) and sulfhydryl reagent (p-chloromercuribenzenesulfonic acid (PCMBS), 100 μM). This accumulation was composed of a saturable component (V(max) = 240 pmol·min-1·μl tissue-1, K(m) = 664 μM) and non-saturable one (P = 0.424 min-1·μl tissue -1). Accumulation of fleroxacin was competitively inhibited by benzylpenicillin and probenecid with K(i) values of 29 μM and 51 μM, respectively. These values are comparable with the K(m) of benzylpenicillin transport and the K(i) of probenecid for the benzylpenicilin transport at the choroid plexus, respectively. Furthermore, fleroxacin inhibited competitively the accumulation of [3H] benzylpenicillin with a K(i) of 384 μM, a value comparable with the K(m) of [14C] fleroxacin transport. Conclusions. Fleroxacin and benzylpenicillin showed mutual competitive inhibition, suggesting that both are transported via a common transport system in the choroid plexus and are pumped out from CSF into the circulation.
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