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Pharmacopsychiatry 2004; 37(6): 292-298
DOI: 10.1055/s-2004-832686
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Modulation of P-Glycoprotein Function by St John’s Wort Extract and its Major Constituents

C. C. Weber1 , S. Kressmann1 , G. Fricker2 , W. E. Müller1
  • 1Department of Pharmacology, Biocenter, University of Frankfurt, Frankfurt, Germany
  • 2Institute of Pharmaceutics and Biopharmacy, University of Heidelberg, Germany
Further Information

Publication History

Received: 6.10.2003 Revised: 5.12.2003

Accepted: 10.12.2003

Publication Date:
19 November 2004 (online)

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Introduction: Recent data suggest some relevant drug interactions caused by St John’s wort extract, which can be explained by interactions with the Cytochrome P450 system or P-Glycoprotein (Pgp). Interaction with Pgp, including activation, inhibition and induction, can lead to altered plasma or brain levels of Pgp substrates. The aim of the present study was to investigate the possible interactions of St John’s wort extract and most relevant constituents with the transport activity of Pgp. Methods: We characterized the modulatory potencies in two in vitro assays using calcein-AM, first in VLB cells (a human lymphocytic leukemia cell line expressing Pgp) and second in PBCEC cells (porcine brain capillary endothelial cells). Results: The extract, as well as some of the tested constituents modulate the transport by Pgp in the micromolecular range. Quercetin and hyperforin seem to be most potent. Conclusions: These findings suggest the possibility of drug interactions at the level of the gastro-intestinal absorption of drugs. Plasma levels of the constituents of St John’s wort are very likely too low to interfere with Pgp at the blood-brain-barrier with the possible exception of quercetin.

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Prof. Dr. W. E. Müller

Department of Pharmacology

Biocenter

Marie-Curie-Str. 9

60439 Frankfurt

Germany

Phone: +49 69 798 29373

Fax: +49 69 798 29374

Email: PharmacolNat@em.uni-frankfurt.de

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