Effect of St. John's wort (Hypericum perforatum) on cytochrome P-450 2D6 and 3A4 activity in healthy volunteers

Life Sci. 2000 Jan 21;66(9):PL133-9. doi: 10.1016/s0024-3205(99)00659-1.


The effects of the herb St. John's wort (Hypericum perforatum), a purported antidepressant, on the activity of cytochrome P-450 (CYP) 2D6 and 3A4 was assessed in seven normal volunteers. Probe substrates dextromethorphan (2D6 activity) and alprazolam (3A4 activity) were administered orally with and without the co-administration of St. John's wort. Urinary concentrations of dextromethorphan and dextrorphan were quantified and dextromethorphan metabolic ratios (DMRs) determined. Plasma samples were collected (0-60 hrs) for alprazolam pharmacokinetic analysis sufficient to estimate tmax, Cmax, t 1/2, and AUC. Validated HPLC methods were used to quantify all compounds of interest. No statistically significant differences were found in any estimated pharmacokinetic parameter for alprazolam or DMRs. These results suggest that St. John's wort, when taken at recommended doses for depression, is unlikely to inhibit CYP 2D6 or CYP 3A4 activity.

MeSH terms

  • Adult
  • Alprazolam / pharmacokinetics
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dextromethorphan / blood
  • Dextromethorphan / pharmacokinetics*
  • Dextrorphan / blood
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Hypericum*
  • Male
  • Mixed Function Oxygenases / metabolism*
  • Plant Extracts / metabolism
  • Plants, Medicinal*


  • Plant Extracts
  • Dextrorphan
  • Dextromethorphan
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • Alprazolam