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Supplementation With Goldenseal (Hydrastis canadensis), but not Kava Kava (Piper methysticum), Inhibits Human CYP3A Activity In Vivo

Gurley, B J, Swain, A, Hubbard, M A, Hartsfield, F, Thaden, J, Williams, D K, Gentry, W B, Tong, Y·2008·Clinical Pharmacology & Therapeutics

DOI 10.1038/sj.clpt.6100222

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Abstract

The effects of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on human CYP3A activity were evaluated using midazolam (MDZ) as a phenotypic probe. Sixteen healthy volunteers were randomly assigned to receive either goldenseal or kava kava for 14 days. Each supplementation phase was followed by a 30-day washout period. MDZ (8 mg, per os) was administered before and after each phase, and pharmacokinetic parameters were determined using standard non-compartmental methods. Comparisons of pre- and post-supplementation MDZ pharmacokinetic parameters revealed significant inhibition of CYP3A by goldenseal (AUC(0-infinity), 107.9+/-43.3 vs 175.3+/-74.8 ng x h/ml; Cl/F/kg, 1.26+/-0.59 vs 0.81+/-0.45 l/h/kg; T(1/2), 2.01+/-0.42 vs 3.15+/-1.12 h; Cmax, 50.6+/-26.9 vs 71.2+/-50.5 ng/ml). MDZ disposition was not affected by kava kava supplementation. These findings suggest that significant herb-drug interactions may result from the concomitant ingestion of goldenseal and CYP3A substrates.

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Authors: Gurley, B. J., Swain, A., Hubbard, M. A., Hartsfield, F., Thaden, J., Williams, D. K., Gentry, W. B., & Tong, Y.
Affiliations: University of Arkansas for Medical Sciences (US)
Corresponding author: Gurley, B J
ORCID: Gurley, B J
Thaden, J
Williams, D K
Tong, Y
Venue: Clinical Pharmacology & Therapeutics
Publisher: Wiley
Published: 2007-05-09
Volume: 83
Issue: 1
Pages: 61-69
ISSN: 0009-9236 (ISSN-L)
1532-6535
DOI: 10.1038/sj.clpt.6100222
OpenAlex: W2103333792
Cited by: 102
References: 46
Citations by year: 2026: 3 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 8 · 2020: 8 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 8 · 2012: 12
FWCI: 3.69
Type: journal article
Language: en
Open access: closed
Locations: Clinical Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (R01GM071322, GM71322)
National Center for Research Resources (M01RR014288, RR-14288)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords: goldenseal, Hydrastis canadensis, kava, CYP3A inhibition, herb-drug interactions, CYP3A substrates
MeSH terms: Adult, Cytochrome P-450 Enzyme System, Enzyme Induction, Enzyme Inhibitors, Female, Humans, Male, Midazolam, Models, Biological, Phenotype, Rifampin, Substrate Specificity, Clarithromycin, Risk Assessment, Dietary Supplements, Kava, Plant Preparations, Hydrastis, Herb-Drug Interactions, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme Inhibitors

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Supplementation With Goldenseal (Hydrastis canadensis), but not Kava Kava (Piper methysticum), Inhibits Human CYP3A Activity In Vivo

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