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Eur J Clin Pharmacol. 2018 Jun;74(6):775-783. doi: 10.1007/s00228-018-2436-2. Epub 2018 Feb 26.

Role of (-)-epigallocatechin gallate in the pharmacokinetic interaction between nadolol and green tea in healthy volunteers.

Author information

1
Department of Pharmacology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
2
Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, Japan.
3
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka, 422-8526, Japan.
4
Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054, Erlangen, Germany.
5
Centre for Medical Education and Career Development, Fukushima Medical University, Fukushima, Japan.
6
Department of Pharmacology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan. misaka@fmu.ac.jp.

Abstract

PURPOSE:

The aim of the present study is to investigate a possible role of a single dose of (-)-epigallocatechin gallate (EGCG), the major catechin in green tea, for the pharmacokinetic interaction between green tea and nadolol in humans.

METHODS:

In a randomized three-phase crossover study, 13 healthy volunteers received single doses of 30 mg nadolol orally with water (control), or an aqueous solution of EGCG-concentrated green tea extract (GTE) at low or high dose. Plasma concentrations and urinary excretion of nadolol were determined up to 48 h. In addition, blood pressure and pulse rate were monitored. In vitro transport kinetic experiments were performed using human embryonic kidney 293 cells stably expressing organic anion transporting polypeptide (OATP)1A2 to evaluate the inhibitory effect of EGCG on OATP1A2-mediated substrate transport.

RESULTS:

Single coadministration of low and high dose GTE significantly reduced the plasma concentrations of nadolol. The geometric mean ratios with 90% CI for area under the plasma concentration-time curves from 0 to infinity of nadolol were 0.72 (0.56-0.87) for the low and 0.60 (0.51-0.69) for the high dose. There were no significant differences in Tmax, elimination half-life, and renal clearance between GTE and water phases. No significant changes were observed for blood pressure and pulse rate between phases. EGCG competitively inhibited OATP1A2-mediated uptake of sulphobromophthalein and nadolol with Ki values of 21.6 and 19.4 μM, respectively.

CONCLUSIONS:

EGCG is suggested to be a key contributor to the interaction of green tea with nadolol. Moreover, even a single coadministration of green tea may significantly affect nadolol pharmacokinetics.

KEYWORDS:

(−)-epigallocatechin gallate; Drug interaction; Green tea; Nadolol; Pharmacokinetics

PMID:
29480324
DOI:
10.1007/s00228-018-2436-2
[Indexed for MEDLINE]

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