European Journal of Clinical Pharmacology

, Volume 62, Issue 1, pp 29–36 | Cite as

The extent of induction of CYP3A by St. John’s wort varies among products and is linked to hyperforin dose

  • Silke C. Mueller
  • Jolanta Majcher-Peszynska
  • Bernhard Uehleke
  • Sebastian Klammt
  • Ralf G. Mundkowski
  • Wolfram Miekisch
  • Hartwig Sievers
  • Steffen Bauer
  • Bruno Frank
  • Guenther Kundt
  • Bernd Drewelow
Pharmacokinetics and Disposition



Induction of CYP3A by St. John’s wort (SJW) extracts with high hyperforin (HYF) content is well described. Since SJW products vary in the amount of HYF and other main constituents, the aim of the study was to evaluate the effect on CYP3A function of SJW preparations with a range from very low to high HYF content.


Forty-two male, healthy volunteers were randomized into six parallel SJW medication groups with varying composition especially with regard to HYF content. Midazolam plasma concentration 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.


All SJW preparations tested resulted in a decrease in midazolam AUC, although the extent of the effect differed. The extract LI 160 (HYF 41 mg/day) decreased midazolam AUC0–12h by 79.4% (95% CI −88.6; −70.1), which was significantly greater than the effect by any other medication (p<0.05). SJW powder tablets 2.7 g/day (HYF 12 mg/day) resulted in a midazolam AUC0–12h decrease of 47.9% (95% CI −59.7;−36.2), while 2.7 g/day SJW powder tablets that were almost devoid of HYF (0.13 mg/day) reduced midazolam AUC0–12h by only 21.1% (95% CI −33.9; −8.3). Considering all six SJW medications tested, the extent of midazolam AUC decrease correlated significantly with increasing HYF dose (r=−0.765, p<0.001), but not with hypericin dose (r=−0.067; p=0.673).


The extent of induction of CYP3A varies among St. John’s wort products and depends on hyperforin dose.


St. John’s wort Hyperforin Hypericins CYP3A Midazolam 



We thank Jana Spaller for organizational assistance, Grit Haase for assistance in taking blood samples and Gunda Hahn, Annette Berg, Patricia Fuchs, Liane Krause and Antje Schümann for processing of samples. The study was supported by funding from companies in Germany that have an interest in St. John’s wort. These companies are: Kneipp Werke, Würzburg; MCM Klosterfrau GmbH, Cologne; Phytolab GmbH, Vestenbergsgreuth; Bad Heilbrunner GmbH, Bad Heilbrunn; Merz Consumer Care GmbH, Frankfurt; GlaxoSmithKline GmbH, Bühl; Salus-Haus, Bruckmühl.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Silke C. Mueller
    • 1
  • Jolanta Majcher-Peszynska
    • 1
  • Bernhard Uehleke
    • 4
  • Sebastian Klammt
    • 1
  • Ralf G. Mundkowski
    • 1
  • Wolfram Miekisch
    • 2
  • Hartwig Sievers
    • 7
  • Steffen Bauer
    • 5
  • Bruno Frank
    • 6
  • Guenther Kundt
    • 3
  • Bernd Drewelow
    • 1
  1. 1.Center of Pharmacology and Toxicology, Institute of Clinical PharmacologyUniversity of RostockRostockGermany
  2. 2.Clinic and Polyclinic of Anaesthesiology and Intensive Care MedicineUniversity of RostockRostockGermany
  3. 3.Institute for Medical Informatics and BiometryUniversity of RostockRostockGermany
  4. 4.Clinic for NaturopathyCharité-Universitätsmedizin BerlinBerlinGermany
  5. 5.Institute of Clinical PharmacologyCharité- Universitätsmedizin BerlinBerlinGermany
  6. 6.Kneipp-WerkeWürzburgGermany
  7. 7.PhytoLab GmbH & Co KGVestenbergsgreuthGermany

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