Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects

• Published in: Clinical pharmacology and therapeutics Vol. 95; no. 4; p. 432
• Main Authors: Misaka, S, Yatabe, J, Müller, F, Takano, K, Kawabe, K, Glaeser, H, Yatabe, M S, Onoue, S, Werba, J P, Watanabe, H, Yamada, S, Fromm, M F, Kimura, J
• Format: Journal Article
• Language: English
• Published: United States 01.04.2014
• Subjects: Adrenergic beta-Antagonists - pharmacokinetics; Adrenergic beta-Antagonists - pharmacology; Adult; Area Under Curve; Blood Pressure - drug effects; Catechin - pharmacokinetics; Cross-Over Studies; Female; Food-Drug Interactions; HEK293 Cells; Humans; Inhibitory Concentration 50; Intestines - metabolism; Male; Nadolol - pharmacokinetics; Nadolol - pharmacology; Organic Anion Transporters - metabolism; Tea - chemistry; Young Adult
• ISSN: 1532-6535
• DOI: 10.1038/clpt.2013.241

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.