Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Effects of Green Tea Compounds on Irinotecan Metabolism

Snezana Mirkov, Bernard J. Komoroski, Jacqueline Ramírez, Andrea Yoder Graber, Mark J. Ratain, Stephen C. Strom and Federico Innocenti
Drug Metabolism and Disposition February 2007, 35 (2) 228-233; DOI: https://doi.org/10.1124/dmd.106.012047
Snezana Mirkov
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernard J. Komoroski
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacqueline Ramírez
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrea Yoder Graber
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark J. Ratain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen C. Strom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Federico Innocenti
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The effects of green tea compounds on the metabolism of irinotecan have never been investigated. We aimed to study whether catechins [(–)-epigallocatechin gallate (EGCG), (–)-epicatechin gallate (ECG), (–)-epigallocatechin (EGC), (–)-epicatechin] affect the inactivation metabolism of irinotecan into 7-ethyl-10-[4-N-(1-piperidino)-1-amino]carbonyloxycamptothecin (NPC) (by CYP3A4) and 7-ethyl-10-hydroxycamptothecin (SN-38) into 7-ethyl-10-hydroxycamptothecin glucuronide (SN-38G) (by UGT1A1). Human liver microsomes, hepatocytes and Hep G2 cells were incubated with catechins and treated with irinotecan and/or SN-38. NPC and SN-38G formation was measured by high-performance liquid chromatography. UGT1A1 mRNA levels were measured by real-time polymerase chain reaction. In human liver microsomes, a concentration-dependent decrease in the formation of NPC and SN-38G was observed. In human hepatocytes, a significant increase in SN-38G production was observed in 33% (EGCG), 44% (ECG), and 44% (EGC) of the hepatocyte preparations. Phenobarbital increased the formation of SN-38G in 100% of the same hepatocyte preparations. In Hep G2 cells, no increase in SN-38G formation was observed. With the exception of ECG in one liver, catechins did not increase UGT1A1 mRNA levels. NPC production was also significantly increased in 40% of the hepatocyte preparations for each catechin. However, the production of 6β-hydroxytestosterone remained unaffected in other hepatocyte preparations. At pharmacologically relevant concentrations, catechins are unlikely to inhibit the formation of irinotecan inactive metabolites when administered concomitantly. The induction effect of catechins on UGT1A1 seems to be modest and highly variable. Catechins do not induce CYP3A4 activity. The effect of acute and prolonged use of green tea on the pharmacokinetics of irinotecan in patients remains to be evaluated.

Footnotes

  • This work was supported by the University of Chicago Cancer Research Center via the Innovative Cancer Complementary and Alternative Medicine Initiative in Cancer Centers Award [NCI P30 CA14599-27S1 (8/1/01–3/31/02)–Innocenti F. (Project P.I.)]. The funded project was entitled “Modulation of Irinotecan Metabolism and Disposition by Green Tea and Soy Extracts.”

  • Preliminary data were presented at the American Society for Clinical Pharmacology and Therapeutics 2004 Annual Meeting, March 24–27, 2004, Miami Beach, FL.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.106.012047.

  • ABBREVIATIONS: EGCG, (–)-epigallocatechin gallate; ECG, (–)-epicatechin gallate; EC, (–)-epicatechin; EGC, (–)-epigallocatechin; SN-38, 7-ethyl-10-hydroxycamptothecin; SN-38G, SN-38-glucuronide; UGT, UDP-glucuronosyltransferase; P450, cytochrome P450; NPC, 7-ethyl-10-[4-N-(1-piperidino)-1-amino]carbonyloxycamptothecin; CPT, camptothecin; HMM, hepatocyte maintenance medium; HMM+, serum-free HMM; PCR, polymerase chain reaction; HPLC, high-performance liquid chromatography; DMSO, dimethyl sulfoxide.

    • Received July 17, 2006.
    • Accepted November 10, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 35 (2)
Drug Metabolism and Disposition
Vol. 35, Issue 2
1 Feb 2007
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Effects of Green Tea Compounds on Irinotecan Metabolism
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Effects of Green Tea Compounds on Irinotecan Metabolism

Snezana Mirkov, Bernard J. Komoroski, Jacqueline Ramírez, Andrea Yoder Graber, Mark J. Ratain, Stephen C. Strom and Federico Innocenti
Drug Metabolism and Disposition February 1, 2007, 35 (2) 228-233; DOI: https://doi.org/10.1124/dmd.106.012047

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

Effects of Green Tea Compounds on Irinotecan Metabolism

Snezana Mirkov, Bernard J. Komoroski, Jacqueline Ramírez, Andrea Yoder Graber, Mark J. Ratain, Stephen C. Strom and Federico Innocenti
Drug Metabolism and Disposition February 1, 2007, 35 (2) 228-233; DOI: https://doi.org/10.1124/dmd.106.012047
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Candesartan glucuronide serves as a CYP2C8 inhibitor
  • Role of AADAC on eslicarbazepine acetate hydrolysis
  • Gene expression profile of human intestinal epithelial cells
Show more Articles

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics