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Beitragstitel Drug cocktail interaction study to investigate the effect of St. John’s wort dry extract Ze 117 on several cytochrome P450 enzymes and on transporter P-glycoprotein in healthy volunteers
Beitragscode P22
  1. Catherine Zahner Zeller Medical AG
  2. Esther Kruttschnitt Zeller Medical AG
  3. Julia Uricher Zeller Medical AG
  4. Michael Lissy Nuvisan GmbH
  5. Martin Hirsch Nuvisan GmbH
  6. Stephan Krähenbühl Universitätsspital Basel
  7. Simon Nicolussi Zeller Medical AG
  8. Jürgen Drewe Zeller Medical AG Vortragender
Präsentationsform Poster
  • 07 - Pharmakotherapie
Abstract Introduction: Hypericum perforatum L. (HP) is a well-documented antidepressant with confirmed efficacy in the treatment of mild to moderate depressive episodes (F32.0-F32.1). A major safety risk limiting its medical use in co-medication are pharmacokinetic (PK) drug interactions caused by hyperforin ( > 1 mg/d) in a dose-dependent manner. Therefore, the low-hyperforin extract Ze117 (Rebalance®) was investigated in a clinical PK drug interaction study.

Methods: In an open, single-sequence cocktail study, the interaction potential of Ze117 was investigated. 7 probe drugs were simultaneously given with and without Ze117. 20 healthy subjects received 500 mg/d Ze117 ( < 1 mg/d hyperforin). Acute inhibition or induction of metabolism was investigated. Blood samples were analysed for parent drug and main metabolite levels. Primary endpoint was AUC.

Results: No evidence of gene-induction was observed considering the plasma levels of probe drugs and their metabolites. Of the 20 subjects included in the study, CYP2D6 genotyping revealed 1 ultrarapid, 1 poor, 3 intermediate and 15 extensive metabolizers. All treatments were well tolerated.

Conclusions: In contrast to data with high-hyperforin extracts of HP no induction of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and P-gp by Ze117 could be found. In summary, these results are in favour of the current expert opinions recommending low-hyperforin HP extracts to alleviate potential unnecessary safety risks in co-medication therapy.