Inhibition of biliary phospholipid and cholesterol secretion by cefoperazone

The effect of cefoperazone, a third-generation cephalosporin, on biliary lipid secretion in rats was examined. Rats were anesthetized with ether and the mid-lumbar vein and common bile duct cannulated. Bile acid secretion was maintained by intravenous taurocholic acid infusion (28 μmol/hr). A 1-hr control period was followed by intravenous cefoperazone infusion at either submaximal (20 μmol/hr), or supramaximal (60 μmol/hr) concentrations. At the cefoperazone infusion rate of 20 μmol/hr (biliary secretion of 7.1±1.6 μmol/hr) phospholipid secretion fell 19% and cholesterol secretion fell 31%; at a cefoperazone infusion rate of 60 μmol/hr (biliary secretion rate of 27.1±5.1 μmol/hr) phospholipid and cholesterol secretion were further reduced 40% and 56%, respectively, of controls. All changes were significant (P<0.01). Inhibition of both cholesterol and phospholipid secretion paralleled each other, was dose-dependent, and reversible. Cefoperazone's inhibitory action was abolished at a bile acid infusion rate of 108 μmol/hr. Cefoperazone was not found to be associated with bile acid micelles or mixed micelles as determined by ultracentrifugation and gel filtration. Thus, the effect of cefoperazone on biliary lipid secretion is not due to the impairment of mixed micelle formation in the canalicular lumen but rather its inhibitory effect appears to be due to a presecretory event.