TY - JOUR
T1 - Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects
AU - Misaka, S.
AU - Yatabe, J.
AU - Müller, F.
AU - Takano, K.
AU - Kawabe, K.
AU - Glaeser, H.
AU - Yatabe, M. S.
AU - Onoue, S.
AU - Werba, J. P.
AU - Watanabe, H.
AU - Yamada, S.
AU - Fromm, M. F.
AU - Kimura, J.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1038/clpt.2013.241
DO - 10.1038/clpt.2013.241
M3 - Article
C2 - 24419562
AN - SCOPUS:84897020921
VL - 95
SP - 432
EP - 438
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 4
ER -