Hyperforin in St. John’s wort drug interactions

  title={Hyperforin in St. John’s wort drug interactions},
  author={Rajanikanth Madabushi and Bruno. Dr Frank and Bernd Drewelow and Hartmut Derendorf and Veronika Butterweck},
  journal={European Journal of Clinical Pharmacology},
Recently, interactions of herbal medicines with synthetic drugs came into focus of particular interest. In the past 3 years, more than 50 papers were published regarding interactions between St. John’s wort (Hypericum perforatum L.; SJW) and prescription drugs. Co-medication with SJW resulted in decreased plasma concentrations of a number of drugs including amitriptyline, cyclosporine, digoxin, indinavir, irinotecan, warfarin, phenprocoumon, alprazolam, dextrometorphane, simvastatin, and oral… 

Clinical relevance of St. John's wort drug interactions revisited

This review revisits the current knowledge of the mechanisms of action and on how pharmacokinetic drug interactions with SJW could be avoided and the degree of CYP3A4 induction correlates significantly with the hyperforin content in the preparation.

Drug Interactions with Herbal Medicines

The present article summarizes herbal medicine-drug interactions involving mainly inhibition or induction of cytochrome P450 enzymes and/or drug transporters and describes the clinical implications of these interactions.

No Clinically Relevant Interactions of St. John's Wort Extract Ze 117 Low in Hyperforin With Cytochrome P450 Enzymes and P‐glycoprotein

Ze 117 does not show clinically relevant pharmacokinetic interactions with important CYPs and P‐glycoprotein, and is well within the predefined bioequivalence range of 80–125%.

Drug–Herb and Drug–Food Interactions

Consumption of a single glass of grapefruit juice caused a twofold to threefold increase in the plasma concentration of felodipine, and pharmocokinetics of approximately 40 other drugs are also affected by intake of Grapefruit juice, and bioavailability of fexofinadine was significantly reduced by grapefruit Juice.

Evaluation of metabolism-mediated herb-drug interactions

Major factors affecting the metabolism of herbal medicines, mechanisms of herb- drug interactions mediated by CYPs and UGTs, and several in vitro methods to assess the herb-drug interactions are described.

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

Administration of an SJW product with low hyperforin content resulted in a mild induction of CYP3A not considered clinically relevant.

Kritische Bewertung und klinische Relevanz

Pharmacokinetic herb-drug interactions are caused by an induction or inhibition of cytochrome P450 (CYP) enzymes or transporters e.g. P-glycoprotein, and a positive in vitro – in vivo correlation regarding the impact on drug bioavailability is rare, results from in vitro studies should be carefully interpreted.

FV 5-2014 notranjost.qxp

At lower doses of St. John’s wort, which are used to relieve mild symptoms, the risk of interactions is not clinically significant and the level of evidence that suggests this possibility is very low.

Interactions Between Herbal Medicines and Prescribed Drugs

Numerous interactions between herbal medicines and conventional drugs have been documented, while the significance of many interactions is uncertain, several interactions, particularly those with St John’s wort, may have serious clinical consequences.



St John's wort (Hypericum perforatum): drug interactions and clinical outcomes.

Possible pharmacodynamic interactions with selective serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such as triptans used to treat migraine were identified and are associated with an increased risk of adverse reactions.

St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor.

  • L. MooreB. Goodwin S. Kliewer
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2000
It is shown that hyperforin, a constituent of St. John's wort with antidepressant activity, is a potent ligand for the pregnane X receptor, an orphan nuclear receptor that regulates expression of the cytochrome P450 (CYP) 3A4 monooxygenase.

Pharmacokinetic Interactions of Drugs with St John’s Wort

The available data indicate that St John’s wort is a potent inducer of CYP 3A4 and P-glycoprotein (PgP), although it may inhibit or induce other CYPs, depending on the dose, route and duration of administration.

Potential Metabolic Interaction between St. John's Wort and Theophylline

The increase in theophylline concentrations observed in this patient after discontinuation of St. John’s wort suggests that components of this herbal supplement may have induced hepatic enzymes (namely, CYP1A2) necessary for theophyLLine clearance.

St Johns wort increases expression of P-glycoprotein: implications for drug interactions.

SJW increased expression and enhanced the drug efflux function of the multi drug transporter P-glycoprotein in PBMCs of healthy volunteers and may represent a second mechanism for the drug-herb interactions seen in clinical practice and account for the discrepancies between in vitro and in vivo data.

No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John's wort extract.

The pharmacokinetic interaction between a low-hyperforin St John's wort extract and alprazolam, caffeine, tolbutamide, and digoxin is evaluated to corroborate the view that reports about interactions of other SJW extracts seem not to be predictive for the product the authors studied.

Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures.

The results demonstrate that with chronic exposure, the inductive effect of SJW on drug-metabolizing enzymes predominates, and human hepatocyte cultures are a versatile in vitro tool for screening the effect of herbal products on cytochrome P450 enzymes.

Drug Interactions with St John’s Wort

  • M. Mannel
  • Medicine
    Canadian family physician Medecin de famille canadien
  • 2001
There is sufficient evidence from interaction studies and case reports to suggest that St John’s wort may induce the cytochrome P450 (CYP) 3A4 enzyme system and the P-glycoprotein drug transporter in a clinically relevant manner, thereby reducing efficacy of co-medications.

Mechanism of Action of St John’s Wort in Depression

This review integrates new findings of possible mechanisms that may underlie the antidepressant action of St John’s wort and its active constituents with a large body of existing literature.