Effects of Green Tea Catechins on Cytochrome P450 2B6, 2C8, 2C19, 2D6 and 3A Activities in Human Liver and Intestinal Microsomes
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- MISAKA Shingen
- Department of Pharmacokinetics and Pharmacodynamics Department of Pharmacology, School of Medicine, Fukushima Medical University
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- KAWABE Keisuke
- Department of Pharmacokinetics and Pharmacodynamics
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- ONOUE Satomi
- Department of Pharmacokinetics and Pharmacodynamics
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- WERBA José Pablo
- Centro Cardiologico Monzino IRCCS
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- GIROLI Monica
- Centro Cardiologico Monzino IRCCS
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- TAMAKI Sekihiro
- Department of Pharmacokinetics and Pharmacodynamics
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- KAN Toshiyuki
- Department of Synthetic Organic and Medicinal Chemistry, School of Pharmaceutical Sciences, University of Shizuoka
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- KIMURA Junko
- Department of Pharmacology, School of Medicine, Fukushima Medical University
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- WATANABE Hiroshi
- Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine
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- YAMADA Shizuo
- Department of Pharmacokinetics and Pharmacodynamics
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Abstract
The effects of green tea catechins on the main drug-metabolizing enzymatic system, cytochrome P450 (CYP), have not been fully elucidated. The objective of the present study was to evaluate the effects of green tea extract (GTE, total catechins 86.5%, w/w) and (−)-epigallocatechin-3-gallate (EGCG) on the activities of CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP3A in vitro, using pooled human liver and intestinal microsomes. Bupropion hydroxylation, amodiaquine N-deethylation, (S)-mephenytoin 4′-hydroxylation, dextromethorphan O-demethylation and midazolam 1′-hydroxylation were assessed in the presence or absence of various concentrations of GTE and EGCG to test their effects on CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP3A activities, respectively. Each metabolite was quantified using UPLC/ESI-MS, and the inhibition kinetics of GTE and EGCG on CYP enzymes was analyzed. In human liver microsomes, IC50 values of GTE were 5.9, 4.5, 48.7, 25.1 and 13.8 µg/mL, for CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP3A, respectively. ECGC also inhibited these CYP isoforms with properties similar to those of GTE, and produced competitive inhibitions against CYP2B6 and CYP2C8, and noncompetitive inhibition against CYP3A. In human intestinal microsomes, IC50 values of GTE and EGCG for CYP3A were 18.4 µg/mL and 31.1 µM, respectively. EGCG moderately inhibited CYP3A activity in a noncompetitive manner. These results suggest that green tea catechins cause clinically relevant interactions with substrates for CYP2B6 and CYP2C8 in addition to CYP3A.<br>
Journal
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 28 (3), 244-249, 2013
The Japanese Society for the Study of Xenobiotics
