ABSTRACT
The effect of the non-selective cyclo-oxygenase inhibitors indomethacin. Diclofenac, sulindac, tolmetin, piroxicam and the selective cyclo-oxygenase type 2 [COX-2] inhibitors celecoxib and rofecoxib on biliary secretion was studied in urethane anaesthetised rats. Drugs were intraperitonealIy administered prior to bile duct cannulation and bile collection. Bile secretions were collected at 30-min intervals for 4 h following drug administration. Bile flow was determined. In addition, total proteins, cholesterol, total, lipids, glucose and several hepatic enzymes were assessed in bile. Results indicated that basal bile secretion was unchanged after diclofenac, but decreased after piroxicam, indomethacin, tolmetin, celecoxib and rotecoxib administration by 23-25%. In contrast, bile flow was increased by 39.3-66.6% after the administration of sulindac. The concentration of cholesterol in bile was increased by all NSAIDs examined. Cholesterol secretion into bile was increased by indomethacin, Piroxicam, high dose sulindac, celecoxib and rofecoxib. All NSAIDs in the study decreased lipid secretion into bile to variable extent. Protein secretion was unchanged by most drugs, but increased by diclofenac and small dose rofecoxib and decreased by tolmetin. These data collectively suggest that NSAIDs alter biliary secretion and composition which is likely to have important clinical implications. Data also suggest that preferential COX-2 inhibition did not result in marked difference compared with conventional NSAIDs as regards the effect on bile flow, cholesterol or biliary lipid secretion