title: Effect of commercial Rhodiola rosea on CYP enzyme activity in humans.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the effect of the herbal drug Rhodiola rosea on the activity of the cytochrome P-450 (CYP) enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in humans.
  
  
  METHODS
  In a randomized cross-over study, 13 healthy volunteers were given a cocktail with single doses of the CYP substrates caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A4) with and without 14 days of pretreatment with a commercially available R. rosea product (Arctic Root, produced by the Swedish Herbal Institute). Four hours after intake of the drug cocktail, a blood sample was obtained, the serum concentrations of the drugs and their metabolites were analyzed, and the metabolic ratios were calculated as a measure of CYP enzyme activity.
  
  
  RESULTS
  A statistically significant 21% decrease in the EXP-3174/losartan ratio was found after pretreatment with R. rosea (p = 0.023), indicating a reduced CYP2C9 metabolic activity. The effect was more pronounced in CYP2C9 extensive metabolizers than in CYP2C9 intermediate and poor metabolizers. For the other CYP enzymes tested, no significant effects were observed.
  
  
  CONCLUSIONS
  This study indicates that R. rosea inhibits the metabolic capacity of CYP2C9 in humans. Although the effect is modest, it might be clinically relevant during treatment with CYP2C9 substrates with a narrow therapeutic index, such as phenytoin and warfarin.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7006, Trondheim, Norway. olekristian.thu@gmail.com.
authors.forename: Ole Kristian
authors.initials: OK
authors.lastname: Thu
authors.affiliation: Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.|Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Spigset
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7006, Trondheim, Norway.
authors.forename: Odd Georg
authors.initials: OG
authors.lastname: Nilsen
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7006, Trondheim, Norway.
authors.forename: Bent
authors.initials: B
authors.lastname: Hellum
mesh_terms: D000328:Adult; D002110:Caffeine / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D003915:Dextromethorphan / Q000493:pharmacokinetics; D004347:Drug Interactions; D006801:Humans; D019808:Losartan / Q000493:pharmacokinetics; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics; D009853:Omeprazole / Q000493:pharmacokinetics; D010936:Plant Extracts / Q000494:pharmacology*; D029771:Rhodiola; D055815:Young Adult
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D010936:Plant Extracts; D002110:Caffeine; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D019808:Losartan; D009853:Omeprazole; D008874:Midazolam
keywords: CYP enzymes; Enzyme inhibition; Healthy volunteers; In vivo; Rhodiola rosea