title: Inhibition of biliary phospholipid and cholesterol secretion by cefoperazone.
abstract: 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 mumol/hr). A 1-hr control period was followed by intravenous cefoperazone infusion at either submaximal (20 mumol/hr), or supramaximal (60 mumol/hr) concentrations. At the cefoperazone infusion rate of 20 mumol/hr (biliary secretion of 7.1 +/- 1.6 mumol/hr) phospholipid secretion fell 19% and cholesterol secretion fell 31%; at a cefoperazone infusion rate of 60 mumol/hr (biliary secretion rate of 27.1 +/- 5.1 mumol/hr) phospholipid and cholesterol secretion were further reduced 40% and 56%, respectively, of controls. All changes were significant (P less than 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 mumol/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.
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D002438:Cefoperazone / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001647:Bile Acids and Salts; D010743:Phospholipids; D002438:Cefoperazone; D002784:Cholesterol