Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin

J Clin Pharmacol. 2006 Feb;46(2):201-13. doi: 10.1177/0091270005284854.

Abstract

Phytochemical-mediated modulation of cytochrome P450 enzymes (CYPs) may underlie many herb-drug interactions. This study's purpose was to assess the effects of milk thistle and black cohosh supplementation on CYP3A activity and compare them to a clinically recognized inducer, rifampin, and inhibitor, clarithromycin. Healthy volunteers were randomly assigned to receive a standardized milk thistle (900 mg) or black cohosh (80 mg) supplement for 14 days. Subjects also received rifampin (600 mg) and clarithromycin (1000 mg) for 7 days as positive controls for CYP3A induction and inhibition, respectively. Midazolam was administered orally before and after each supplementation and control period. The effects of milk thistle, black cohosh, rifampin, and clarithromycin on midazolam pharmacokinetics were determined using noncompartmental techniques. Unlike those observed for rifampin and clarithromycin, midazolam pharmacokinetics was unaffected by milk thistle or black cohosh. Milk thistle and black cohosh appear to have no clinically relevant effect on CYP3A activity in vivo.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacology*
  • Antibiotics, Antitubercular / pharmacology*
  • Area Under Curve
  • Cimicifuga / chemistry*
  • Clarithromycin / pharmacology*
  • Cytochrome P-450 CYP3A / biosynthesis
  • Cytochrome P-450 CYP3A / metabolism*
  • Cytochrome P-450 CYP3A Inhibitors
  • Dietary Supplements*
  • Drug Interactions
  • Enzyme Activators / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Hypnotics and Sedatives / pharmacokinetics
  • Male
  • Midazolam / pharmacokinetics
  • Milk Thistle / chemistry*
  • Phenotype
  • Rifampin / pharmacology*
  • Sex Characteristics

Substances

  • Anti-Bacterial Agents
  • Antibiotics, Antitubercular
  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Activators
  • Enzyme Inhibitors
  • Hypnotics and Sedatives
  • Cytochrome P-450 CYP3A
  • Clarithromycin
  • Midazolam
  • Rifampin