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Cerebrospinal fluid (CSF) concentrations of quinolone antibiotics in humans, which may be related to CNS adverse effects and quinolone antibiotic-induced convulsions, were predicted from parameters for penetration into the CSF (CSF-to-unbound plasma concentration ratio : Kpu) of rats and dogs. There was good linear correlation between the Kpu values for rats and dogs (r=0.94), and the relative magnitude of Kpu values among the quinolone antibiotics examined was not affected by the species difference. The CSF concentrations (CCSF, Pred) in humans that were predicted from the Kpu values in rats and dogs were well correlated with the CSF concentrations (CCSF, Obs) actually observed in humans (r=0.86 and 0.91, respectively). These results suggest that for clinical doses, CSF quinolone concentrations in humans can be predicted from Kpu values in animals. The CSF concentrations of UFX (an active metabolite of a prodrug, prulifloxacin), norfloxacin, and ciprofloxacin were lower than those of other quinolone antibiotics.

iryō yakugaku/iryou yakugaku

Prediction of Cerebrospinal Fluid Concentrations of Quinolone Antibiotics in Humans Using Parameters for Penetration into Cerebrospinal Fluid of Animals