Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 95, Issue 4, Pages 432-438Publisher
WILEY
DOI: 10.1038/clpt.2013.241
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Funding
- Japanese Ministry of Education, Culture, Sports, Science, and Technology [23790605]
- Grants-in-Aid for Scientific Research [23790605] Funding Source: KAKEN
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This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the beta-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. [H-3]-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 mu mol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated nadolol uptake (half-maximal inhibitory concentration, IC50 = 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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