Ole Kristian Thu1, Olav Spigset2,3, Odd Georg Nilsen4, Bent Hellum4. 1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7006, Trondheim, Norway. olekristian.thu@gmail.com. 2. Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway. 3. Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. 4. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7006, Trondheim, Norway.
Abstract
PURPOSE: 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.
RCT Entities:
PURPOSE: 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: Alexander G Panossian; Thomas Efferth; Alexander N Shikov; Olga N Pozharitskaya; Kenny Kuchta; Pulok K Mukherjee; Subhadip Banerjee; Michael Heinrich; Wanying Wu; De-An Guo; Hildebert Wagner Journal: Med Res Rev Date: 2020-10-25 Impact factor: 12.944
Authors: Alexander Bertuccioli; Marco Cardinali; Francesco Di Pierro; Simone Magi; Giordano Zonzini Journal: J Med Food Date: 2021-11-17 Impact factor: 2.786