St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.

Autor: El Biali M; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.; Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland., Wölfl-Duchek M; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.; Department of Biomedical Imaging und Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria., Jackwerth M; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria., Mairinger S; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.; Department of Biomedical Imaging und Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria., Weber M; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria., Bamminger K; Department of Biomedical Imaging und Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria., Poschner S; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria., Rausch I; QIMP Team, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria., Schindler N; Department of Biomedical Imaging und Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria., Lozano IH; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria., Jäger W; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria., Nics L; Department of Biomedical Imaging und Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria., Tournier N; Laboratoire d'Imagerie Biomédicale Multimodale (BIOMAPS), Université Paris-Saclay, CEA, CNRS, Inserm, Service Hospitalier Frédéric Joliot, Orsay, France., Hacker M; Department of Biomedical Imaging und Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria., Zeitlinger M; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria., Bauer M; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria., Langer O; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.; Department of Biomedical Imaging und Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
Jazyk: angličtina
Zdroj: Clinical and translational science [Clin Transl Sci] 2024 May; Vol. 17 (5), pp. e13804.
DOI: 10.1111/cts.13804
Abstrakt: St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs. In this study, we used a combination of positron emission tomography (PET) imaging and cocktail phenotyping to gain a comprehensive picture on the effect of SJW on central and peripheral P-gp and CYP activities. Before and after treatment of healthy volunteers (n = 10) with SJW extract with a high hyperforin content (3-6%) for 12-19 days (1800 mg/day), the activity of P-gp at the BBB was assessed by means of PET imaging with the P-gp substrate [ 11 C]metoclopramide and the activity of peripheral P-gp and CYPs was assessed by administering a low-dose phenotyping cocktail (caffeine, omeprazole, dextromethorphan, and midazolam or fexofenadine). SJW significantly increased peripheral P-gp, CYP3A, and CYP2C19 activity. Conversely, no significant changes in the peripheral metabolism, brain distribution, and P-gp-mediated efflux of [ 11 C]metoclopramide across the BBB were observed following the treatment with SJW extract. Our data suggest that SJW does not lead to significant P-gp induction at the human BBB despite its ability to induce peripheral P-gp and CYPs. Simultaneous intake of SJW with CNS-targeted P-gp substrate drugs is not expected to lead to P-gp-mediated drug interactions at the BBB.
(© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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