4beta-hydroxycholesterol as an endogenous marker for CYP3A4/5 activity. Stability and half-life of elimination after induction with rifampicin

Br J Clin Pharmacol. 2009 Jan;67(1):38-43. doi: 10.1111/j.1365-2125.2008.03309.x. Epub 2008 Nov 6.


Aims: The oxysterol 4beta-hydroxycholesterol has been suggested as a marker for CYP3A4/5 activity. We have previously shown that plasma 4beta-hydroxycholesterol continues to increase for several weeks after maximal induction of CYP3A4/5 by carbamazepine at the dose given. In the present study we aimed to determine the time course of the decrease in plasma 4beta-hydroxycholesterol after termination of induction of CYP3A4/5 by rifampicin. An additional aim was to determine the variation in plasma level of 4beta-hydroxycholesterol with time in 12 untreated healthy volunteers.

Methods: Twenty-four healthy subjects were allocated into three study groups of equal sizes. The volunteers were treated with rifampicin (either 20 mg day(-1), 100 mg day(-1) or 500 mg day(-1)) for 2 weeks. Blood samples were taken before, during and after rifampicin treatment. In another group of 12 untreated volunteers blood samples were collected at different time points in order to determine the intraindividual variations in plasma 4beta-hydroxycholesterol concentrations. Plasma levels of 4beta-hydroxycholesterol were determined by isotope-dilution gas chromatography-mass spectrometry.

Results: Rifampicin treatment increased plasma 4beta-hydroxycholesterol levels. After termination of rifampicin treatment plasma levels of 4beta-hydroxycholesterol decreased slowly with an apparent half-life of 17 days. The intraindividual variation in plasma levels of 4beta-hydroxycholesterol in untreated subjects was low, with coefficients of variation of between 4.8 and 13.2% over a period of 3 months.

Conclusions: After termination of induction of CYP3A4/5, plasma 4beta-hydroxycholesterol levels decreased slowly during 8 weeks. The half-life of elimination (17 days) resembled that of cholesterol rather than other oxysterols. The long half-life results in stable plasma concentrations with time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP3A Inhibitors*
  • Enzyme Inhibitors / pharmacology*
  • Gas Chromatography-Mass Spectrometry / methods
  • Half-Life
  • Humans
  • Hydroxycholesterols / metabolism*
  • Rifampin / pharmacology*


  • Biomarkers
  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Inhibitors
  • Hydroxycholesterols
  • cholest-5-ene-3,4-diol
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Rifampin