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  • Title: Stimulation of bile acid 6 alpha-hydroxylation by rifampin.
    Author: Wietholtz H, Marschall HU, Sjövall J, Matern S.
    Journal: J Hepatol; 1996 Jun; 24(6):713-8. PubMed ID: 8835747.
    Abstract:
    BACKGROUND: Rifampin was shown to relieve pruritus in cholestatic liver diseases. There has been much speculation about the origin of pruritus, but it has not yet been comprehensively explained. The role of bile acids in producing pruritus is obscure and still under debate. Since rifampin both inhibits the uptake of bile acids into the hepatocyte and strongly induces mixed-function oxidases in the liver, the beneficial effects of this drug might be a consequence of altered bile acid metabolism. METHODS: We investigated the influence of rifampin on urinary bile acid excretion with special respect to glucuronide and sulphate conjugates in 14 healthy volunteers before and after administration of rifampin, 600 mg x 7 days, using each subject as his or her own control. RESULTS: Bile acid glucuronide excretion increased from 0.55 to 1.19 mumol/24 h. This was in particular due to a significant increase of the urinary excretion of the 6 alpha-hydroxylated hyocholic and hyodeoxycholic acids, the relative amounts of which accounted for about two thirds of the urinary bile acid excretion. Excretion of sulphates, however, decreased from 1.40 to 0.86 mumol/24 h due to a significantly reduced excretion of lithocholic acid sulphate. No changes in the excretion rates of other primary and secondary bile acids and no changes in their conjugation patterns were observed. CONCLUSIONS: The results provide evidence that rifampin induces 6 alpha-hydroxylation of bile acids. The products are subsequently glucuronidated at the 6 alpha-hydroxy group, thus stimulating renal excretion of potentially toxic bile acids.
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