Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • 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
  • Submit
  • 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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • 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
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Abstract

Organ-specific pattern of inhibition of diltiazem metabolism at steady state in rabbits.

M Lefebvre, G Caillé and P du Souich
Journal of Pharmacology and Experimental Therapeutics November 1996, 279 (2) 902-907;
M Lefebvre
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G Caillé
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P du Souich
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Plasma levels of diltiazem, after its chronic administration, are usually higher than predicted. Because several organs contribute to diltiazem metabolism, this study aimed to determine the effect of an infusion of diltiazem to steady state on the ability of the intestine, liver and lungs to metabolize diltiazem and its metabolites N-desmethyldiltiazem (MA) and desacetyldiltiazem (M1). The kinetics of diltiazem were assessed after a single i.v. injection (2 mg/kg) and after an infusion (1.4 mg/kg/hr over 15 hr) of diltiazem. After serial blood sampling, the rabbits were sacrificed, and diltiazem, MA and M1 constant rates of metabolism (Kmet) were estimated in the 10,000 x g supernatants of the intestinal mucosa, liver and lungs. In vivo, the systemic clearance of infused diltiazem was lower than that estimated after i.v. injection of diltiazem, i.e., 54.4 +/- 2.4 vs. 70.3 +/- 5.8 ml/min/kg (P < .05). In vitro, diltiazem Kmet was reduced in liver homogenates from rabbits that had received the infusion of diltiazem, but not in the intestine or lungs. Moreover, the production of MA was reduced in liver homogenates and that of M1 in intestinal and lung homogenates. The Kmet of MA was not affected by the infusion of diltiazem in any tissue studied; however, the Kmet of M1 was reduced by the infusion in the three tissues tested. It is concluded that, in rabbits, long-term administration of diltiazem leads to an accumulation of diltiazem primarily because its N-demethylation is decreased in the liver, in addition, the demethylation of M1 is reduced in the small intestine, liver and lungs.

JPET 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

Journal of Pharmacology and Experimental Therapeutics
Vol. 279, Issue 2
1 Nov 1996
  • Table of Contents
  • Table of Contents (PDF)
  • 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 Journal of Pharmacology and Experimental Therapeutics 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.
Organ-specific pattern of inhibition of diltiazem metabolism at steady state in rabbits.
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Abstract

Organ-specific pattern of inhibition of diltiazem metabolism at steady state in rabbits.

M Lefebvre, G Caillé and P du Souich
Journal of Pharmacology and Experimental Therapeutics November 1, 1996, 279 (2) 902-907;

Citation Manager Formats

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

Share
Abstract

Organ-specific pattern of inhibition of diltiazem metabolism at steady state in rabbits.

M Lefebvre, G Caillé and P du Souich
Journal of Pharmacology and Experimental Therapeutics November 1, 1996, 279 (2) 902-907;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

Similar Articles

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

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics