Norfloxacin binds to human fecal material

Area of Science:

• Microbiology
• Pharmacology
• Gastroenterology

Background:

• High fecal concentrations of norfloxacin are observed after therapeutic doses, yet the gastrointestinal microflora remains largely unaffected.
• The minimum inhibitory concentrations (MICs) for fecal microorganisms are typically lower than these observed fecal concentrations.

Purpose of the Study:

• To investigate the binding of norfloxacin to fecal material.
• To explore the interaction between norfloxacin, fecal content, and specific gut bacteria like *Enterococcus faecium* and *Bacteroides fragilis*.

Main Methods:

• Radiolabeled [14C]norfloxacin was used to analyze binding to fecal material.
• Binding assays were performed with various unlabeled quinolones and bacterial suspensions.
• Scatchard plots and nonlinear regression were employed for binding analysis.

Main Results:

• Norfloxacin demonstrated significant binding to feces, characterized by specific and unspecific binding classes with distinct dissociation constants (KD) and maximal binding capacities (Bmax).
• Binding was reversible, saturated within 90 minutes at 37°C, and increased with fecal concentration.
• Norfloxacin binding was primarily associated with the bacterial fraction of feces, particularly *Bacteroides fragilis*.
• The presence of *B. fragilis* significantly increased the minimum bactericidal concentration (MBC) of norfloxacin against *E. faecium*.

Conclusions:

• The binding of norfloxacin to fecal material, especially bacteria, can explain the discrepancy between high fecal drug concentrations and its limited impact on the gut microflora.
• This binding phenomenon is a crucial factor in the pharmacodynamics of norfloxacin within the gastrointestinal tract.