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Int J Clin Pharmacol Ther. 2004 Jun;42(6):307-13.

Influence of rifampin on serum markers of cholesterol and bile acid synthesis in men.

Author information

1
Department of Clinical Pharmacology, University of Bonn, Germany. d.luetjohann@uni-bonn.de

Abstract

OBJECTIVE:

It has been demonstrated in preliminary studies that rifampin, a semisynthetic antibiotic and known inducer of hepatic cytochrome P450 3A4, reduces serum concentrations of total bile acids only in individuals with liver disease and elevated serum bile acid levels.

METHODS:

We studied the effect of rifampin on concentrations of surrogate serum markers of cholesterol and bile acid synthesis as well as of cholesterol absorption in 10 male subjects before and after administration of rifampin (600 mg/day) for 6 days. Cholesterol and its precursors were analyzed by gas-liquid chromatography (GLC), bile acid intermediates and individual bile acids by isotope-dilution methods using GLC-mass spectrometry (MS) or by high-performance liquid chromatography (HPLC).

RESULTS:

Treatment with rifampin resulted in a 70% increase (p = 0.008) of the serum concentration of the bile acid precursor 7alpha-hydroxy-4-cholesten-3-one, which is a marker for bile acid production. Serum total cholesterol was not altered, however, treatment with rifampin elevated the ratio of lathosterol to cholesterol, an indicator of cholesterol synthesis, by 23% (p = 0.037). Interestingly, serum concentration of total bile acids decreased slightly by 29% (p = 0.022), mainly due to a lowering of the secondary bile acid, deoxycholic acid (-60%; p = 0.005).

CONCLUSION:

A 6-day treatment with rifampin induces a reduction of deoxycholic serum concentrations in healthy men associated with a moderate increase of serum markers of bile acid and endogenous cholesterol synthesis.

PMID:
15222722
DOI:
10.5414/cpp42307
[Indexed for MEDLINE]

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