Effects of Green Tea Catechins on Cytochrome P450 2B6, 2C8, 2C19, 2D6 and 3A Activities in Human Liver and Intestinal Microsomes

doi:10.2133/dmpk.DMPK-12-RG-101

Drug Metabolism and Pharmacokinetics

Volume 28, Issue 3, 2013, Pages 244-249

https://doi.org/10.2133/dmpk.DMPK-12-RG-101 Get rights and content

Summary:

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 non-competitive inhibition against CYP3A. In human intestinal microsomes, IC₅₀ values of GTE and EGCG for CYP3A were 18.4 μg/mL and 31.1 μΜ, 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.

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: This work was supported in part by a Grant-in-Aid for JSPS Fellows (No. 21–55522) from the Japan Society for the Promotion of Science; and Project of Shizuoka Prefecture and Shizuoka City Collaboration of Regional Entities for the Advancement of Technological Excellence, Japan Science and Technology Agency (JST).

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Regular ArticleEffects of Green Tea Catechins on Cytochrome P450 2B6, 2C8, 2C19, 2D6 and 3A Activities in Human Liver and Intestinal Microsomes

Summary:

Adv. Drug Deliv. Rev.

Prev. Med.

Life Sci.

Mutat. Res.

Drug Metab. Pharmacokinet.

Biochem. Pharmacol.

Prev. Med.

Clinical relevance of the small intestine as an organ of drug elimination: drug-fruit juice interactions

Expert Opin. Drug Metab. Toxicol.

Interaction between grapefruit juice and midazolam in humans

Clin. Pharmacol. Ther.

Identification of 6′,7′-dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice

Drug Metab. Dispos.

Cancer prevention by tea: animal studies, molecular mechanisms and human relevance

Nat. Rev. Cancer

Effects of green tea catechins and theanine on preventing influenza infection among healthcare workers: a randomized controlled trial

BMC Complement. Altern. Med.

Metabolism of green tea catechins: an overview

Curr. Drug Metab.

Green tea (Camellia sinensis) extract does not alter cytochrome p450 3A4 or 2D6 activity in healthy volunteers

Drug Metab. Dispos.

Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam

Psychopharmacology (Berlin)

Effects of repeated green tea catechin administration on human cytochrome P450 activity

Cancer Epidemiol. Biomarkers Prev.

The effect of green tea on simvastatin tolerability

Ann. Intern. Med.

Regular Article
Effects of Green Tea Catechins on Cytochrome P450 2B6, 2C8, 2C19, 2D6 and 3A Activities in Human Liver and Intestinal Microsomes