title: The supplement-drug interaction of quercetin with tamsulosin on vasorelaxation.
abstract: The food supplement quercetin is used as self-medication for prostate disorders and is known to induce vasorelaxation. The drug tamsulosin is used in the treatment of benign prostatic hyperplasia. A major side effect of tamsulosin is orthostatic hypotension, mediated by vasorelaxation resulting from α1-adrenoceptor blockade. The overlapping profile prompted us to investigate the pharmacodynamic interaction of quercetin with tamsulosin. Since quercetin is extensively metabolized in the intestines and the liver, the metabolites quercetin-3-glucuronide and 4'O-methyl-quercetin were also examined. Vasorelaxation induced by the compounds was tested in rat mesenteric arteries (average diameter: 360±μm) constricted by the α1-adrenoceptor agonist phenylephrine. Tamsulosin (0.1nM) decreased phenylephrine sensitivity 17-fold (n=10). Quercetin (5, 10 and 20µM) also caused a decrease (2-, 4- and 6-fold respectively) of phenylephrine sensitivity, while 10µM of quercetin-3-glucuronide and 4'O-methyl-quercetin decreased this sensitivity (1.5- and 2-fold) only slightly (n=6). The combination of tamsulosin with quercetin or quercetin metabolites proved to be far more potent than the compounds in isolation. The combination of quercetin, quercetin-3-glucuronide or 4'O-methyl-quercetin with tamsulosin decreased the phenylephrine sensitivity approximately 200-, 35- and 150-fold (n=6). The strong pharmacodynamic interaction between the food supplement quercetin and tamsulosin underlines the potential of the impact of supplement-drug interactions that warrant more research.
authors.affiliation: Department of Toxicology and Pharmacology, Maastricht University, Maastricht, The Netherlands. Electronic address: m.vrolijk@maastrichtuniversity.nl.
authors.forename: Misha F
authors.initials: MF
authors.lastname: Vrolijk
authors.affiliation: Department of Toxicology and Pharmacology, Maastricht University, Maastricht, The Netherlands. Electronic address: g.haenen@maastrichtuniversity.nl.
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
authors.affiliation: Department of Toxicology and Pharmacology, Maastricht University, Maastricht, The Netherlands; Netherlands Food and Consumer Product Safety Authority (NVWA), Utrecht, The Netherlands.
authors.forename: Antoon
authors.initials: A
authors.lastname: Opperhuizen
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Eugène H J M
authors.initials: EH
authors.lastname: Jansen
authors.affiliation: Department of Toxicology and Pharmacology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Schiffers
authors.affiliation: Department of Toxicology and Pharmacology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D004347:Drug Interactions; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011794:Quercetin / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D000077409:Tamsulosin; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D013449:Sulfonamides; D010656:Phenylephrine; D011794:Quercetin; D006861:Hydrogen Peroxide; D000077409:Tamsulosin
keywords: 4′O-methyl-quercetin (PubChem CID 5281699); Orthostatic hypotension; Pharmacodynamics; Quercetin; Quercetin (PubChem CID 5280343); Quercetin-3-glucuronide (PubChem CID 5274585); Supplement–drug interaction; Tamsulosin; Tamsulosin (PubChem CID 129211); Vasorelaxation