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

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

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.

Methods

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.

Results

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).

Conclusion

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

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Acknowledgements

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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Authors and Affiliations

  1. Center of Pharmacology and Toxicology, Institute of Clinical Pharmacology, University of Rostock, Schillingallee 70, 18057, Rostock, Germany

    Silke C. Mueller, Jolanta Majcher-Peszynska, Sebastian Klammt, Ralf G. Mundkowski & Bernd Drewelow

  2. Clinic and Polyclinic of Anaesthesiology and Intensive Care Medicine, University of Rostock, Schillingallee 35, 18057, Rostock, Germany

    Wolfram Miekisch

  3. Institute for Medical Informatics and Biometry, University of Rostock, Rembrandtstrasse 16/17, 18057, Rostock, Germany

    Guenther Kundt

  4. Clinic for Naturopathy, Charité-Universitätsmedizin Berlin, Königstrasse 63, 14109, Berlin, Germany

    Bernhard Uehleke

  5. Institute of Clinical Pharmacology, Charité- Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117, Berlin, Germany

    Steffen Bauer

  6. Kneipp-Werke, Steinbachtal 43, 97064, Würzburg, Germany

    Bruno Frank

  7. PhytoLab GmbH & Co KG, Dutendorfer Strasse 5–7, 91487, Vestenbergsgreuth, Germany

    Hartwig Sievers

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  1. Silke C. Mueller
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  2. Jolanta Majcher-Peszynska
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  11. Bernd Drewelow
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Corresponding author

Correspondence to Silke C. Mueller.

Additional information

The study was started after approval by the ethics committee of the University of Rostock and was performed according to the national laws of Germany.

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Mueller, S.C., Majcher-Peszynska, J., Uehleke, B. et al. The extent of induction of CYP3A by St. John’s wort varies among products and is linked to hyperforin dose. Eur J Clin Pharmacol 62, 29–36 (2006). https://doi.org/10.1007/s00228-005-0061-3

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  • DOI: https://doi.org/10.1007/s00228-005-0061-3

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