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Earlier studies have reported very high (120 to 2,700 mg/kg) concentrations of norfloxacin in feces after therapeutic doses. MICs for fecal microorganisms are with few exceptions far below these levels. Nevertheless, clinical investigations show that the main part of the aerobic gram-positive and the anaerobic microflora remains unaffected after norfloxacin administration. In this study, the binding of [14C]norfloxacin to fecal material was analyzed. The binding of a group of nonlabeled quinolones to feces and the interactions between Enterococcus faecium, Bacteroides fragilis, and norfloxacin were also investigated. The results showed that norfloxacin has the ability to bind to feces. The specific binding was reversible, saturated after 90 min of incubation at 37 degrees C, and increased linearly with fecal concentration. Scatchard plots and nonlinear regression computer analyses revealed two different binding classes. The primary specific binding had a dissociation constant (KD) of 1.0 microM and a maximal binding capacity (Bmax) of 0.12 mumol/g of feces. The KD and Bmax of the secondary, more unspecific binding were 450 microM and 11.8 mumol/g of feces, respectively. The binding of unlabeled ciprofloxacin, enoxacin, ofloxacin, pefloxacin, and norfloxacin to feces was comparable to that of [14C]norfloxacin. The results of norfloxacin binding to suspensions of B. fragilis suggested that the main part of the binding is to the bacterial fraction of feces. In the presence of 8.0 g (dry weight) of B. fragilis per liter, the MBC of norfloxacin for E. faecium increased from 8 to 256 micrograms/ml. The finding of the present study indicated that binding of norfloxacin to feces may explain the paradox of high fecal concentrations of norfloxacin versus the actual effect on the normal gastrointestinal microflora.

Norfloxacin binds to human fecal material