Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI119439

Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.

K S Lown, D G Bailey, R J Fontana, S K Janardan, C H Adair, L A Fortlage, M B Brown, W Guo, and P B Watkins

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

Find articles by Lown, K. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

Find articles by Bailey, D. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

Find articles by Fontana, R. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

Find articles by Janardan, S. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

Find articles by Adair, C. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

Find articles by Fortlage, L. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

Find articles by Brown, M. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

Find articles by Guo, W. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

Find articles by Watkins, P. in: JCI | PubMed | Google Scholar

Published May 15, 1997 - More info

Published in Volume 99, Issue 10 on May 15, 1997
J Clin Invest. 1997;99(10):2545–2553. https://doi.org/10.1172/JCI119439.
© 1997 The American Society for Clinical Investigation
Published May 15, 1997 - Version history
View PDF
Abstract

The increase in oral availability of felodipine and other commonly used medications when taken with grapefruit juice has been assumed to be due to inhibition of CYP3A4, a cytochrome P450 that is present in liver and intestine. To evaluate the effect of repeated grapefruit juice ingestion on CYP3A4 expression, 10 healthy men were given 8 oz of grapefruit juice three times a day for 6 d. Before and after receiving grapefruit juice, small bowel and colon mucosal biopsies were obtained endoscopically, oral felodipine kinetics were determined, and liver CYP3A4 activity was measured with the [14C N-methyl] erythromycin breath test in each subject. Grapefruit juice did not alter liver CYP3A4 activity, colon levels of CYP3A5, or small bowel concentrations of P-glycoprotein, villin, CYP1A1, and CYP2D6. In contrast, the concentration of CYP3A4 in small bowel epithelia (enterocytes) fell 62% (P = 0.0006) with no corresponding change in CYP3A4 mRNA levels. In addition, enterocyte concentrations of CYP3A4 measured before grapefruit juice consumption correlated with the increase in Cmax when felodipine was taken with either the 1st or the 16th glass of grapefruit juice relative to water (r = 0. 67, P = 0.043, and r = 0.71, P = 0.022, respectively). We conclude that a mechanism for the effect of grapefruit juice on oral felodipine kinetics is its selective downregulation of CYP3A4 in the small intestine.

Version history
  • Version 1 (May 15, 1997): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts