Determination and pharmacokinetic study of unbound cefepime in rat bile by liquid chromatography with on-line microdialysis

Biliary excretion and intestinal reabsorption in enterohepatic circulation play major dispositional roles for some drugs. To investigate biliary excretion of drug, we inserted a microdialysis probe into the bile common duct of rat between the liver and the duodenum. In order to avoid the obstruction of bile fluid or bile salt waste, a shunt linear microdialysis probe was used for simultaneous and continuous sampling following intravenous administration of cefepime (50 mg/kg, i.v.). Separation and quantitation of cefepime in the dialysates were achieved using a LiChrosorb RP-18 column (Merck; 250×4.6 mm I.D., particle size 5 μm) maintained at ambient temperature. Samples were eluted with a mobile phase containing 100 mM monosodium phosphoric acid (pH 3.0)–methanol (87:13, v/v). The UV detector wavelength was set at 270 nm. The result indicates that the elimination half-life of cefepime in bile was 64.01±9.32 min. This study also served as an example for the microdialysis application in the biliary excretion study of drug.