St. John’s wort without drug interactions?

Accumulating scientific evidence from clinical studies suggests that the well-known drug interaction potential of Hypericum perforatum, L. (St. John’s wort) is based on one single constituent: hyperforin.

Hyperforin is detected by the human body as a troublesome substance by the « Xenosenor » PXR in the intestine and liver. As a consequence, metabolic enzymes and transport systems are activated to eliminate such substances including also other drugs. This is the reason for drug interactions with St. John’s wort, where in co-medication therapy concomitant essential drugs may become ineffective. Over the past 20 years, several cases of transplant rejections, lack of drug efficacy or unwanted pregnancies in association with St. John’s wort have been published. For years it was unknown why these drug interactions occured.

In a new pharmakokinetic interaction study the low-hyperforin St. John’s wort dry extract Ze 117 was investigated in 20 healthy subjects. In a Phase I, open-label, non-randomized, single-sequence study, Ze 117 was taken together with a cocktail of several probe drugs to investigate Cytochrome P450 (CYP) and P-glycoprotein related drug interactions. As a result, no clinically relevant drug interactions were observed for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and P-gp.

This is the world’s first 7 probe drug cocktail interaction study investigation with St. John’s wort providing comprehensive evidence of a major advantage in drug safety for low-hyperforin extracts.

https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt.1392

The results of this cocktail-study are in line with expert opinions and recommendations by health authorities to use low-hyperforin St. John’s wort extracts to reduce the unnecessary risk of drug interactions and thereby increase safety for the patients during the treatment of depressive episodes.

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Zahner C, Kruttschnitt E, Uricher J, Lissy M, Hirsch M, et al. 2019. No clinically relevant interactions of St. John's wort extract Ze 117 low in hyperforin with cytochrome P450 enzymes and P-glycoprotein. Clin Pharmacol Ther