Disposition of ciprofloxacin in the isolated perfused rat liver.
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.
Abadìa
A R
AR
Experimental Liver Toxicology Unit, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
De Francesco
L
L
Guaitani
A
A
D000818:Animals; D001646:Bile / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism; D001711:Biotransformation; D002939:Ciprofloxacin / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D002939:Ciprofloxacin