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

John S. Markowitz, C. L. DeVane, D. W. Boulton, S. W. Carson, Z. Nahas, S. C. Risch

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149 Scopus citations

Abstract

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 t(max), C(max), 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. (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)PL133-PL139
JournalLife Sciences
Volume66
Issue number9
DOIs
StatePublished - Jan 21 2000

Keywords

  • Cytochrome P-450
  • Drug interaction
  • Herb
  • Hypericum perforatum
  • St. John's wort

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