Biliary elimination of indomethacin in man.

The biliary elimination of indomethacin 100 mg p.o. has been investigated in patients with a T-tube drain after cholecystectomy, who had normal or abnormal liver function (Group I n = 5, and Group II n = 4, respectively). In plasma, the concentration maximum (Group I 9.5 +/- 1.4 mumol X l-1; Group II 19.4 +/- 3.8 mumol X l-1) and the total clearance (Group I 1.56 +/- 0.28 ml X min-1 X kg-1, Group II 0.5 +/- 0.06 ml X min-1 X kg-1) were significant different in the two groups. The bile:plasma ratio (bpr) in Group I was 1.3 +/- 0.33 and 10.1 +/- 3.2, respectively, for indomethacin (In) and conjugated In. The conjugated fraction of In was 87.5 +/- 1.9% of the total concentration. In Group II the bpr was lower (0.65 +/- 0.1). In is eliminated in bile by diffusion and conjugated In by active secretion. In Group I 0.99 +/- 0.1 mg In and 6.1 +/- 0.7 mg conjugated In and in Group II 2.1 +/- 0.3 mg In (p less than 0.05) were eliminated in bile. No influence of In on the biliary lipids was observed or on the bile acid-independent fraction of bile flow. It is concluded that the total plasma clearance of In was dependent of liver function. Conjugated In undergoes enterohepatic circulation.