STIMULATION OF BILE-ACID 6-ALPHA-HYDROXYLATION BY RIFAMPIN

Background: Rifampin was shown to relieve pruritus in cholestatic live r diseases. There has been much speculation about the origin of prurit us, but it has not yet been comprehensively explained. The role of bil e acids in producing pruritus is obscure and still under debate. Since rifampin both inhibits the uptake of bile acids into the hepatocyte a nd strongly induces mixed-function oxidases in the liver, the benefici al effects of this drug might be a consequence of altered bile acid me tabolism. Methods: We investigated the influence of rifampin on urinar y bile acid excretion with special respect to glucuronide and sulphate conjugates in 14 healthy volunteers before and after administration o f rifampin, 600 mgx7 days, using each subject as his or her own contro l. Results: Bile acid glucuronide excretion increased from 0.55 to 1.1 9 mu mol/24 h. This was in particular due to a significant increase of the urinary excretion of the 6 alpha-hydroxylated hyocholic and hyode oxycholic acids, the relative amounts of which accounted for about two thirds of the urinary bile acid excretion. Excretion of sulphates, ho wever, decreased from 1.40 to 0.86 mu mol/24 h due to a significantly reduced excretion of lithocholic acid sulphate. No changes in the excr etion rates of other primary and secondary bile acids and no changes i n their conjugation patterns were observed. Conclusions: The results p rovide evidence that rifampin induces 6 alpha-hydroxylation of bile ac ids. The products are subsequently glucuronidated at the 6 alpha-hydro xy group, thus stimulating renal excretion of potentially toxic bile a cids.