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

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

Clinical pharmacology and therapeutics (2014-01-15)
S Misaka, J Yatabe, F Müller, K Takano, K Kawabe, H Glaeser, M S Yatabe, S Onoue, J P Werba, H Watanabe, S Yamada, M F Fromm, J Kimura
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
(−)-Epicatechin, ≥90% (HPLC)
Sigma-Aldrich
(−)-Epicatechin, ≥98% (HPLC), from green tea
Epicatechin, primary reference standard
Supelco
(−)-Epicatechin, analytical standard
Supelco
Nadolol, analytical standard
Supelco
(+)-Catechin, analytical standard
Nadolol, European Pharmacopoeia (EP) Reference Standard