Effect of Fenbufen on the Entry of New Quinolones, Norfloxacin and Ofloxacin, into the Central Nervous System in Rats

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Abstract
The entry of two new quinolone antibacterial agents, norfloxacin and ofloxacin, into the central nervous system (CNS) of rats, and the effect of fenbufen on this was investigated. At various times after the administration of a bolus intravenous dose of norfloxacin or ofloxacin (10 mg kg−1) with or without fenbufen (20 mg kg−1), serum and cerebrospinal fluid (CSF) samples and whole brain were collected from the rats and the concentration of norfloxacin or ofloxacin in each sample was determined. Serum concentrations of both quinolones declined biexponentially with time and were significantly elevated by coadministration with fenbufen at the terminal phase. The fractions of these quinolones bound to serum protein were not altered by coadministration with fenbufen. Coadministered fenbufen raised the brain concentrations of both quinolones but did not affect their brain to serum unbound concentration ratios. In contrast, CSF to serum unbound concentration ratios as well as CSF concentrations of norfloxacin and ofloxacin were elevated by coadministration with fenbufen. Apparent diffusional clearances between blood and CSF of norfloxacin and ofloxacin estimated by the physiological model analysis increased by 1·9 and 2·6 times, respectively, after coadministration with fenbufen. These findings suggest that coadministered fenbufen may facilitate the entry of norfloxacin and ofloxacin into the CNS.