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
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
    • 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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleArticle

Modulation of Effect of Dietary Salt on Prehepatic First-Pass Metabolism: Effects of β-Blockade and Intravenous Salt Loading

Martin F. Fromm, Dawood Darbar, Simonetta Dell’Orto and Dan M. Roden
Journal of Pharmacology and Experimental Therapeutics July 1999, 290 (1) 253-258;
Martin F. Fromm
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dawood Darbar
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simonetta Dell’Orto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dan M. Roden
  • 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

We previously demonstrated that increased dietary salt markedly decreases plasma quinidine concentrations shortly after p.o. dosing, without an effect on the drug’s terminal elimination half-life or concentrations after i.v. administration. These findings suggest an effect of dietary salt on intestinal metabolism or transport of the drug. Because one effect of salt loading is sympathetic inhibition, we examined the effect of β-adrenoceptor blockade on salt-related changes in quinidine disposition. Furthermore, we examined whether the action of salt is local or systemic by determining the effect of salt loading by the i.v. route. To assess the effect of β-blockade, quinidine disposition was studied in eight normal volunteers after a single p.o. dose of quinidine; data were obtained after 1 week on a high-salt diet (400 mEq/day) and 1 week on a low-salt diet (10 mEq/day) during chronic nadolol and compared with those previously obtained in the same subjects without the β-blocker. β-Blockade had no effect on oral clearance during the high-salt diet [0.28 ± 0.1 (quinidine + nadolol) versus 0.30 ± 0.2 liters/h/kg (quinidine alone)] but increased clearance on the low-salt diet from 0.23 ± 0.1 to 0.29 ± 0.1 liters/h/kg (p < .05). For the i.v. salt study, the disposition of single p.o. and single i.v. doses of quinidine was determined on two occasions in eight subjects: once during a low-salt diet (10 mEq/day) and once during the same diet, supplemented by 400 mEq/day NaCl i.v. for 8 days. In contrast to our findings after p.o. salt loading, i.v. salt loading did not alter the pharmacokinetics of p.o. quinidine. Taken together, these data implicate a local alteration of drug-metabolizing activity and/or drug transport in the intestinal mucosa as the major effect of dietary salt on the disposition of p.o. quinidine and further suggest that β-adrenergic activation by a low-salt diet is one component of a signaling pathway whereby intestinal drug disposition is suppressed, resulting in increased oral bioavailability.

Footnotes

  • Send reprint requests to: Dan M. Roden, M.D., Division of Clinical Pharmacology, 532 Medical Research Building-I, Vanderbilt University School of Medicine, Nashville, TN 37232. E-mail:dan.roden{at}mcmail.vanderbilt.edu

  • ↵1 This work was supported in part by U.S. Public Health Service Grants GM31304, GM07569, and RR095. Dr. Fromm was supported by the Deutsche Forschungsgemeinschaft (Fr 1298/1-1, Bonn, Germany). Dr. Roden is the holder of the William Stokes Chair in Experimental Therapeutics, a gift of Daiichi Pharmaceutical.

  • ↵2 These authors contributed equally to the study.

  • Abbreviations:
    AUC
    area under the time-concentration curve
    AUCi.v.
    area under the plasma concentration-time curve after i.v. administration
    AUCp.o.
    area under the plasma concentration-time curve after p.o. administration
    CL
    clearance
    CLO
    apparent oral clearance
    CLS
    systemic clearance
    Cmax
    maximum quinidine concentration
    CYP
    cytochrome P-450
    t1/2
    terminal elimination half-life
    Tmax
    time to reach maximum concentration
    F
    bioavailability
    VC
    volume of distribution
    • Received July 24, 1998.
    • Accepted March 1, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

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: 290 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 290, Issue 1
1 Jul 1999
  • Table of Contents
  • About the Cover
  • Index by author
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.
Modulation of Effect of Dietary Salt on Prehepatic First-Pass Metabolism: Effects of β-Blockade and Intravenous Salt Loading
(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
Research ArticleArticle

Modulation of Effect of Dietary Salt on Prehepatic First-Pass Metabolism: Effects of β-Blockade and Intravenous Salt Loading

Martin F. Fromm, Dawood Darbar, Simonetta Dell’Orto and Dan M. Roden
Journal of Pharmacology and Experimental Therapeutics July 1, 1999, 290 (1) 253-258;

Citation Manager Formats

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

Modulation of Effect of Dietary Salt on Prehepatic First-Pass Metabolism: Effects of β-Blockade and Intravenous Salt Loading

Martin F. Fromm, Dawood Darbar, Simonetta Dell’Orto and Dan M. Roden
Journal of Pharmacology and Experimental Therapeutics July 1, 1999, 290 (1) 253-258;
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
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CRV431 Decreases Liver Fibrosis and Tumor Development
  • Discriminative Stimulus Effects of Zolpidem in Squirrel Monkeys: Comparison with Conventional Benzodiazepines and Sedative-Hypnotics
  • Powerful Activation of Skeletal Muscle Actomyosin ATPase by Goniodomin A Is Highly Sensitive to Troponin/Tropomyosin Complex
Show more Article

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 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics