title: Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops.
abstract: METHODS
  Women seeking alternatives to hormone-replacement therapy for menopausal symptoms often try botanical dietary supplements containing extracts of hops (Humulus lupulus L.). Hops contain 8-prenylnaringenin (8-PN), a potent phytoestrogen, the related flavanones 6-prenylnaringenin and isoxanthohumol (IX), and the prenylated chalcone xanthohumol (XN).
  
  
  RESULTS
  After chemically and biologically standardizing an extract of spent hops to these marker compounds, an escalating dose study was carried out in menopausal women to evaluate safety and pharmacokinetics. 8-PN, 6-prenylnaringenin, IX, and XN, sex hormones, and prothrombin time were determined in blood samples and/or 24 h urine samples. There was no effect on sex hormones or blood clotting. The maximum serum concentrations of the prenylated phenols were dose-dependent and were reached from 2 to 7 h, indicating slow absorption. The marker compounds formed glucuronides that were found in serum and urine. Secondary peaks at 5 h in the serum concentration-time curves indicated enterohepatic recirculation. The serum concentration-time curves indicated demethylation of IX to form 8-PN and cyclization of XN to IX. Slow absorption and enterohepatic recirculation contributed to half-lives exceeding 20 h.
  
  
  CONCLUSIONS
  This human study indicated long half-lives of the estrogenic and proestrogenic prenylated phenols in hops but no acute toxicity.
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, IL, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: van Breemen
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.forename: Suzanne
authors.initials: S
authors.lastname: Banuvar
authors.forename: Lee P
authors.initials: LP
authors.lastname: Shulman
authors.forename: Xi
authors.initials: X
authors.lastname: Qiu
authors.forename: René F Ramos
authors.initials: RF
authors.lastname: Alvarenga
authors.forename: Shao-Nong
authors.initials: SN
authors.lastname: Chen
authors.forename: Birgit M
authors.initials: BM
authors.lastname: Dietz
authors.forename: Judy L
authors.initials: JL
authors.lastname: Bolton
authors.forename: Guido F
authors.initials: GF
authors.lastname: Pauli
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Krause
authors.forename: Marlos
authors.initials: M
authors.lastname: Viana
authors.forename: Dejan
authors.initials: D
authors.lastname: Nikolic
mesh_terms: D000368:Aged; D001515:Beer; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects / Q000032:analysis / Q000191:economics; D004764:Enterohepatic Circulation; D005260:Female; D005525:Food-Processing Industry / Q000191:economics; D020719:Glucuronides / Q000097:blood / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D007220:Industrial Waste / Q000032:analysis / Q000191:economics; D056626:Inflorescence / Q000737:chemistry*; D007408:Intestinal Absorption; D007700:Kinetics; D008745:Methylation; D008875:Middle Aged; D010636:Phenols / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000378:metabolism*; D048789:Phytoestrogens / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000378:metabolism*; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D017698:Postmenopause; D054876:Prenylation
chemical_list: D015415:Biomarkers; D020719:Glucuronides; D007220:Industrial Waste; D010636:Phenols; D048789:Phytoestrogens; D010936:Plant Extracts
keywords: 8-Prenylnaringenin; Hops; Isoxanthohumol; Pharmacokinetics; Xanthohumol