Phenobarbital-induced alterations of bile acid metabolism in cases of intrahepatic cholestasis.
Bile acid profiles from plasma and urine of six patients suffering from intrahepatic cholestasis were studied before and during treatment with phenobarbital. All patients responded to this treatment by decreasing their plasma bile acid levels. Using gas chromatographic and mass spectrometric methods for separation and identification of the bile acids, especially the occurrence of major atypical bile acids was quantitatively evaluated. The plasma bile acid lowering effect of phenobarbital in intrahepatic cholestasis can be partly explained by an increased formation of tetrahydroxylated bile acids, which are rapidly excreted by renal pathways. These tetrahydroxylated bile acids, present as nonsulfated compounds, have high renal excretory flow rates exceeding those of bile acid sulfates. Their enterohepatic circulation, however, seems to be low, since only small amounts of tetrahydroxylated bile acids can be found in bile. It is mainly the 1- and 6-hydroxylation that is stimulated by phenobarbital. The exact site of formation of tetrahydroxylated bile acids, however, is still unknown. These findings may provide a rationale for the institution of a phenobarbital treatment in cases of intrahepatic cholestasis.
D000293:Adolescent; D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000627:therapeutic use*
D001647:Bile Acids and Salts; D010634:Phenobarbital