Detaillierte Beitrags-Information
| 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 |
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| Beitragscode | P22 |
| Autoren | |
| Präsentationsform | Poster |
| Themengebiete |
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| 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. |