Cefixime is a new orally effective third-generation cephalosporin. It inhibits a wide variety of Gram-positive and Gram-negative bacteria, especially most of the Enterobacteriaceae. Since extrarenal excretion processes have been reported to account for 60% of cefixime systemic clearance we have endeavoured to determine the place taken up by biliary excretion of unchanged cefixime in this pattern. We initially used the isolated perfused rabbit liver technique. Six perfusions were performed. Cefixime concentrations were measured by HPLC chromatography. After addition of a single 10-mg dose of cefixime to the circulating blood, biliary elimination of the drug proved to be very low, since only 0.28 +/- 0.15% of the dose was recovered during the 3-h perfusion period. The rate of cefixime biotransformation in the liver was found to be 16.2%. In contrast, the data obtained in humans highlight substantial biliary excretion of the drug. In six healthy volunteers submitted to duodenal aspiration and receiving a single 200-mg i.v. dose of cefixime, drug levels in duodenal fluid were at least fivefold greater than the simultaneous concentrations in serum. Biliary excretion of cefixime was further investigated in ten cholecystectomized patients provided with T-tube drainage: following a single 200 mg oral dose of cefixime, Cmax in bile reached 56.9 +/- 70 mg/l, that is about 25 times as high as Cmax in serum, 2.3 +/- 0.85 mg/l. Drug levels in choledochal bile proved to be sustained, since a concentration of 4.3 +/- 3.7 mg/ml was still observed 20 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)