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. 2019 Aug;106(2):432-440. doi: 10.1002/cpt.1392. Epub 2019 Mar 23.


Hypericum perforatum L. (St. John's wort) is used to treat mild-to-moderate depression. Its potential safety risks are pharmacokinetic drug interactions via cytochrome P450 (CYP) enzymes and P-glycoprotein, presumably caused by hyperforin. In a phase I, open-label, nonrandomized, single-sequence study, the low-hyperforin Hypericum extract Ze 117 was investigated using a drug cocktail in 20 healthy volunteers. No pharmacokinetic interactions of Ze 117 were observed for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, and P-glycoprotein. Area under the curve (AUC) and peak plasma concentration (Cmax ) of the used probe drugs showed 90% confidence intervals (CIs) of the geometric mean ratios of the drugs taken together with Ze 117 vs. probe drug alone, well within the predefined bioequivalence range of 80-125%. Though Ze 117 did not induce dextromethorphan metabolism by CYP2D6, it weakly increased dextromethorphan AUC ratio (mean 147.99, 95% CI 126.32-173.39) but not the corresponding metabolic ratio. Ze 117 does not show clinically relevant pharmacokinetic interactions with important CYPs and P-glycoprotein.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adult
  • Area Under Curve
  • Cytochrome P-450 Enzyme System* / genetics
  • Cytochrome P-450 Enzyme System* / metabolism
  • Dextromethorphan / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Interactions*
  • Female
  • Healthy Volunteers
  • Humans
  • Hypericum / metabolism
  • Male
  • Phloroglucinol / analogs & derivatives*
  • Phloroglucinol / pharmacokinetics
  • Plant Extracts / pharmacokinetics*
  • Psychotropic Drugs / pharmacokinetics
  • Terpenes / pharmacokinetics*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Plant Extracts
  • Psychotropic Drugs
  • Terpenes
  • ZE 117
  • Dextromethorphan
  • Cytochrome P-450 Enzyme System
  • Phloroglucinol
  • hyperforin