Dose ranging pharmacokinetics and brain distribution of norfloxacin using microdialysis in rats

The purpose of this study was to investigate the effect of dose on norfloxacin pharmacokinetics and distribution into the brain extracellular fluid (ECF), in freely moving rats. Unbound concentrations of norfloxacin in hippocampus were determined by microdialysis after an i.v. bolus dose of 12.5, 25, 50, 100, or 150 mg/kg in rats. In vivo recovery of norfloxacin was determined by retrodialysis by calibrator. Among three fluoroquinolones (enoxacin, pefloxacin, and ciprofloxacin) selected as potential calibrators, ciprofloxacin was selected as the best one. Maximum ECF brain norfloxacin concentrations are rapidly obtained but the ECFbrain/plasma areas under curves (AUC) ratios are low and independent of dose with a mean value of 8.2 +/- 5.8%. By contrast, norfloxacin systemic pharmacokinetics was nonlinear, with total plasma clearance decreasing significantly from 23.0 +/- 3.4 to 14.4 +/- 3.8 mL/min/kg when dose increased from 12.5 to 150 mg/kg.