title: Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects.
abstract: This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the β-blocker nadolol. Ten healthy volunteers received a single oral dose of 30 mg nadolol with green tea or water after repeated consumption of green tea (700 ml/day) or water for 14 days. Catechin concentrations in green tea and plasma were determined. Green tea markedly decreased the maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-48)) of nadolol by 85.3% and 85.0%, respectively (P < 0.01), without altering renal clearance of nadolol. The effects of nadolol on systolic blood pressure were significantly reduced by green tea. [(3)H]-Nadolol uptake assays in human embryonic kidney 293 cells stably expressing the organic anion-transporting polypeptides OATP1A2 and OATP2B1 revealed that nadolol is a substrate of OATP1A2 (Michaelis constant (K(m)) = 84.3 μmol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated nadolol uptake (half-maximal inhibitory concentration, IC(50) = 1.36%). These results suggest that green tea reduces plasma concentrations of nadolol possibly in part by inhibition of OATP1A2-mediated uptake of nadolol in the intestine.
authors.affiliation: 1] Department of Pharmacology, School of Medicine, Fukushima Medical University, Fukushima, Japan [2] Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Misaka
authors.affiliation: Department of Pharmacology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Yatabe
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Müller
authors.affiliation: Department of Pharmacology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takano
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawabe
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Glaeser
authors.affiliation: Department of Pharmacology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: M S
authors.initials: MS
authors.lastname: Yatabe
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Onoue
authors.affiliation: Centro Cardiologico Monzino IRCCS, Milan, Italy.
authors.forename: J P
authors.initials: JP
authors.lastname: Werba
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: M F
authors.initials: MF
authors.lastname: Fromm
authors.affiliation: Department of Pharmacology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kimura
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D002392:Catechin / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D009248:Nadolol / Q000493:pharmacokinetics* / Q000494:pharmacology; D027361:Organic Anion Transporters / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D027361:Organic Anion Transporters; C512988:SLCO1A2 protein, human; C450859:SLCO2B1 protein, human; D013662:Tea; D009248:Nadolol; D002392:Catechin