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

  • 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) 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 AUC0–∞ 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 Cmax, t1/2 and tmax 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.

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Acknowledgements

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

Conflicts of interest statement:

Dr. H. Sievers and Dr. R. Lehnfeld are employees of Phytolab GmbH, and Dr. B. Frank is an employee of Kneipp Werke. Both companies have an interest in St. John’s wort. The other authors declared no conflict of interest.

Author information

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, Ralf G. Mundkowski, Sebastian Klammt & Bernd Drewelow

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

    Guenther Kundt

  3. Department of Naturopathy, Universitätsmedizin Berlin, CBF, Hindenburgdamm 30, 12203, Berlin, Germany

    Bernhard Uehleke

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

    Bruno Frank

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

    Hartwig Sievers & Romanus Lehnfeld

  6. Center for Life Science Automation, University of Rostock, Friedrich-Barnewitz-Str. 8, 18119, Rostock, Germany

    Kerstin Thurow

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  1. Silke C. Mueller
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Correspondence to Silke C. Mueller.

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Mueller, S.C., Majcher-Peszynska, J., Mundkowski, R.G. et al. No clinically relevant CYP3A induction after St. John’s wort with low hyperforin content in healthy volunteers. Eur J Clin Pharmacol 65, 81–87 (2009). https://doi.org/10.1007/s00228-008-0554-y

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  • DOI: https://doi.org/10.1007/s00228-008-0554-y

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