Abstract

Ciprofloxacin (CIP), a quinolone with a wide spectrum of antibacterial activity, was studied in the isolated perfused rat liver. Three concentrations (1, 5, and 25 mg/liter) were used in the perfusion medium to check whether hepatic transformation and/or biliary elimination of this drug was dose-dependent. Pharmacokinetic parameters of CIP in the perfusion medium were similar when normalized for the dose at all three concentrations. Some dose-dependent changes were observed in biliary excretion of CIP. CIP biliary clearance and the percentage of excreted drug differed at 25 mg/liter and the lower concentrations. In addition, the chromatograms of the bile samples at the highest dose showed a peak that never appeared at the lower concentrations. This evidence, together with the zwitterion characteristics of CIP, reaching a bile/medium area under the concentration-time curve ratio > 10, suggests that an active transport mechanism is involved in the drug's biliary excretion, as has been demonstrated for its renal elimination.