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.
© 2019 Max Zeller & Söhne AG. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.