Possibility for induction of convulsion by fleroxacin and its disposition in the central nervous system in animals

Fleroxacin and its metabolites were examined for their possibility of the induction of convulsion in mice, inhibitory activity on GABA receptor binding, and disposition in the central nervous system of mice, rats and dogs. No convulsion was evoked in mice at high oral combination doses of fleroxacin and fenbufen. Brain-to-serum concentration ratios of fleroxacin after oral dose were 0.13 in mice, 0.19 in rats and 0.28 in dogs. Rats showed no accumulation of fleroxacin in brain and similar elimination from brain to that from serum after the oral dose. Dogs exhibited the similar distribution of fleroxacin into various brain regions. The inhibitory effect of fleroxacin on GABA receptor binding was relatively weak and slightly potentiated in the presence of 4-biphenylacetic acid. Demethyl fleroxacin showed more potent inhibitory activity on GABA receptor binding and potentiation with 4-biphenylacetic acid. The combination of intravenous demethyl fleroxacin and oral fenbufen showed no convulsion in mice. Fleroxacin N-oxide showed only slight inhibitory activity on GABA receptor binding, being not influenced with 4-biphenylacetic acid.