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
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
    • 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 dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

MODULATION OF THE P-GLYCOPROTEIN-MEDIATED INTESTINAL SECRETION OF IVERMECTIN: IN VITRO AND IN VIVO ASSESSMENTS

M. Ballent, A. Lifschitz, G. Virkel, J. Sallovitz and C. Lanusse
Drug Metabolism and Disposition March 2006, 34 (3) 457-463; DOI: https://doi.org/10.1124/dmd.105.007757
M. Ballent
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. Lifschitz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G. Virkel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Sallovitz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Lanusse
  • 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 everted gut sac method was used to assess the role of the P-glycoprotein (P-gp) on the intestinal secretion of ivermectin (IVM), an antiparasitic widely used in human and veterinary medicine. The work included the evaluation of two different P-gp modulators [itraconazole (ITZ) and valspodar (PSC833)] used at equimolar doses in the rat. Furthermore, the influence of both P-gp modulator agents on the disposition kinetics of IVM in plasma, liver, and gastrointestinal tissues was characterized. For the in vitro experiments, ileal sacs were incubated with IVM (3 μM) in the presence or absence of either ITZ (10 μM) or PSC833 (10 μM). In the in vivo experiments, male Wistar rats were randomly allocated to three groups (n = 18) and subcutaneously treated with IVM (200 μg/kg–1), alone and coadministered with ITZ (5 mg, two doses) or PSC833 (8.6 mg, two doses). Animals were sacrificed between 6 and 96 h. Blood, liver, and gastrointestinal samples were collected. IVM concentrations were determined by high performance liquid chromatography. The rate of IVM accumulation in the intestinal wall of everted sacs was significantly higher after its incubation with ITZ (0.115 nmol/g/min) and PSC833 (0.238 nmol/g/min) than that obtained after the incubation without the P-gp modulators (0.016 nmol/g/min). In agreement with the in vitro experiment, the presence of ITZ and PSC833 induced an enhancement in the concentrations of IVM in plasma and gastrointestinal tissues. The results obtained in the current work, both under in vivo and in vitro conditions, confirm the relevance of P-gp-mediated transport to the intestinal secretion of IVM.

Footnotes

  • Research at the Laboratorio de Farmacología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro (Tandil, Argentina) is partially supported by the Agencia Nacional de Promoción Científica y Tecnológica, Secretaría de Ciencia y Técnica, Universidad Nacional del Centro and Fundación Antorchas.

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

  • doi:10.1124/dmd.105.007757.

  • ABBREVIATIONS: P-gp, P-glycoprotein; PSC833, valspodar; IVM, ivermectin; ITZ, itraconazole; HPLC, high performance liquid chromatography; AUC, area under the concentration-time curve.

    • Received October 12, 2005.
    • Accepted December 19, 2005.
  • 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: 34 (3)
Drug Metabolism and Disposition
Vol. 34, Issue 3
1 Mar 2006
  • 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.
MODULATION OF THE P-GLYCOPROTEIN-MEDIATED INTESTINAL SECRETION OF IVERMECTIN: IN VITRO AND IN VIVO ASSESSMENTS
(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

MODULATION OF THE P-GLYCOPROTEIN-MEDIATED INTESTINAL SECRETION OF IVERMECTIN: IN VITRO AND IN VIVO ASSESSMENTS

M. Ballent, A. Lifschitz, G. Virkel, J. Sallovitz and C. Lanusse
Drug Metabolism and Disposition March 1, 2006, 34 (3) 457-463; DOI: https://doi.org/10.1124/dmd.105.007757

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 THE P-GLYCOPROTEIN-MEDIATED INTESTINAL SECRETION OF IVERMECTIN: IN VITRO AND IN VIVO ASSESSMENTS

M. Ballent, A. Lifschitz, G. Virkel, J. Sallovitz and C. Lanusse
Drug Metabolism and Disposition March 1, 2006, 34 (3) 457-463; DOI: https://doi.org/10.1124/dmd.105.007757
Reddit logo Twitter logo Facebook 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

  • Cytochrome P450 4F11 in lung cancer
  • SLC49A4-mediated pyrilamine transport
  • Functional Characterization of 29 CYP4F2 Variants
Show more Articles

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 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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics