No clinically relevant CYP3A induction after St. John's wort with low hyperforin content in healthy volunteers

Eur J Clin Pharmacol. 2009 Jan;65(1):81-7. doi: 10.1007/s00228-008-0554-y. Epub 2008 Sep 3.

Abstract

Objective: Induction of CYP3A by St. John's wort (SJW) products with high hyperforin content is well described. Since CYP3A induction is mediated by hyperforin in a concentration-dependent manner, and SJW preparations differ significantly in hyperforin content, the aim of the study was to evaluate the effect of an SJW powder with low hyperforin content on CYP3A function.

Methods: Twenty healthy male volunteers received an SJW powder with low hyperforin content for 2 weeks. Midazolam plasma concentration time profiles were characterized after a single oral dose of 7.5 mg midazolam on the day before and on the 14th day of SJW medication.

Results: Midazolam AUC(0-infinity) slightly decreased from 124.0 +/- 62.5 ng/ml.h at baseline to 105.6 +/- 53.2 ng/ml.h after SJW (P < 0.05), representing a mean 11.3% decrease (95% CI: -22.8 to 0.21). No significant change in midazolam C(max), t(1/2) and t(max) was observed. For all pharmacokinetic parameters, the 90% CI for the geometric mean ratio of treatment over baseline were within the no-effect boundaries of 0.70-1.43.

Conclusion: Administration of an SJW product with low hyperforin content resulted in a mild induction of CYP3A not considered clinically relevant.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Bridged Bicyclo Compounds / administration & dosage
  • Bridged Bicyclo Compounds / analysis
  • Bridged Bicyclo Compounds / pharmacology
  • Cross-Over Studies
  • Cytochrome P-450 CYP3A / biosynthesis*
  • Enzyme Induction
  • Herb-Drug Interactions
  • Humans
  • Hypericum*
  • Male
  • Midazolam / administration & dosage
  • Midazolam / pharmacokinetics
  • Phloroglucinol / administration & dosage
  • Phloroglucinol / analogs & derivatives*
  • Phloroglucinol / analysis
  • Phloroglucinol / pharmacology
  • Plant Preparations / administration & dosage
  • Plant Preparations / chemistry
  • Plant Preparations / pharmacology*
  • Powders
  • Substrate Specificity
  • Terpenes / administration & dosage
  • Terpenes / analysis
  • Terpenes / pharmacology*
  • Young Adult

Substances

  • Bridged Bicyclo Compounds
  • Plant Preparations
  • Powders
  • Terpenes
  • Phloroglucinol
  • Cytochrome P-450 CYP3A
  • Midazolam
  • hyperforin