Pharmacokinetic Interactions of a Hop Dietary Supplement with Drug Metabolism in Perimenopausal and Postmenopausal Women
- Richard B. van Breemen*Richard B. van Breemen*Email: [email protected]. Phone: 541-737-5078. Fax: 541-737-5077.Linus Pauling Institute, College of Pharmacy, Oregon State University, 2900 SW Campus Way, Corvallis, Oregon 97331, United StatesUIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United StatesMore by Richard B. van Breemen,
- Luying ChenLuying ChenLinus Pauling Institute, College of Pharmacy, Oregon State University, 2900 SW Campus Way, Corvallis, Oregon 97331, United StatesUIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United StatesMore by Luying Chen,
- Alyssa Tonsing-CarterAlyssa Tonsing-CarterClinical and Healthcare Research Policy Division, National Institutes of Health, 6705 Rockledge Dr., Suite 750, Bethesda, Maryland 20817, United StatesUIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United StatesMore by Alyssa Tonsing-Carter,
- Suzanne BanuvarSuzanne BanuvarUIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United StatesMore by Suzanne Banuvar,
- Elena BarengoltsElena BarengoltsUIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United StatesMore by Elena Barengolts,
- Marlos VianaMarlos VianaUIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United StatesMore by Marlos Viana,
- Shao-Nong ChenShao-Nong ChenUIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United StatesMore by Shao-Nong Chen,
- Guido F. PauliGuido F. PauliUIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United StatesMore by Guido F. Pauli, and
- Judy L. BoltonJudy L. BoltonUIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United StatesMore by Judy L. Bolton
Abstract
Botanical dietary supplements produced from hops (Humulus lupulus) containing the chemopreventive compound xanthohumol and phytoestrogen 8-prenylnaringenin are used by women to manage menopausal symptoms. Because of the long half-lives of prenylated hop phenols and reports that they inhibit certain cytochrome P450 enzymes, a botanically authenticated and chemically standardized hop extract was tested for Phase I pharmacokinetic drug interactions. Sixteen peri- and postmenopausal women consumed the hop extract twice daily for 2 weeks, and the pharmacokinetics of tolbutamide, caffeine, dextromethorphan, and alprazolam were evaluated before and after supplementation as probe substrates for the enzymes CYP2C9, CYP1A2, CYP2D6, and CYP3A4/5, respectively. The observed area under the time–concentration curves were unaffected, except for alprazolam which decreased 7.6% (564.6 ± 46.1 h·μg/L pre-hop and 521.9 ± 36.1 h·μg/L post-hop; p-value 0.047), suggesting minor induction of CYP3A4/5. No enzyme inhibition was detected. According to FDA guidelines, this hop dietary supplement caused no clinically relevant pharmacokinetic interactions with respect to CYP2C9, CYP1A2, CYP2D6, or CYP3A4/5. The serum obtained after consumption of the hop extract was analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry to confirm compliance. Abundant Phase II conjugates of the hop prenylated phenols were observed including monoglucuronides and monosulfates as well as previously unreported diglucuronides and sulfate-glucuronic acid diconjugates.
Cited By
This article is cited by 4 publications.
- Luying Chen, Jaewoo Choi, Scott W. Leonard, Suzanne Banuvar, Elena Barengolts, Marlos Viana, Shao-Nong Chen, Guido F. Pauli, Judy L. Bolton, Richard B. van Breemen. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. Journal of Agricultural and Food Chemistry 2020, 68 (47) , 13929-13939. https://doi.org/10.1021/acs.jafc.0c05856
- Lance Buckett, Sabrina Schönberger, Veronika Spindler, Nadine Sus, Christian Schoergenhofer, Jan Frank, Oliver Frank, Michael Rychlik. Synthesis of Human Phase I and Phase II Metabolites of Hop (Humulus lupulus) Prenylated Flavonoids. Metabolites 2022, 12 (4) , 345. https://doi.org/10.3390/metabo12040345
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- Kurt Lucas, Janine Fröhlich-Nowoisky, Nicole Oppitz, Maximilian Ackermann. Cinnamon and Hop Extracts as Potential Immunomodulators for Severe COVID-19 Cases. Frontiers in Plant Science 2021, 12 https://doi.org/10.3389/fpls.2021.589783