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

Transport of l-Valine-Acyclovir Via the Oligopeptide Transporter In The Human Intestinal Cell Line, Caco-2

Remco L. A. de Vrueh, Philip L. Smith and Chao-Pin Lee
Journal of Pharmacology and Experimental Therapeutics September 1998, 286 (3) 1166-1170;
Remco L. A. de Vrueh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip L. Smith
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chao-Pin Lee
  • 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

It has been reported that conjugating acyclovir, a potent antiviral with low oral bioavailability, to l-valine increases its urinary excretion in rats. However, it was also reported that this increase is not found for the d-valine ester, suggesting that a carrier-mediated mechanism is involved in its intestinal absorption. Therefore, mechanisms involved in the transepithelial transport of l-valine-acyclovir were investigated using the intestinal cell line, Caco-2, as a model system for the intestinal epithelium. Only the mucosal-to-serosal transport of acyclovir was increased by conjugation with l-valine (∼7-fold), suggesting the involvement of a carrier-mediated mechanism. This conclusion was supported by the finding that this increase was saturable. The mucosal-to-serosal transport ofl-valine-acyclovir could be inhibited byl-glycylsarcosine, but not by l-valine, suggesting the involvement of the dipeptide carrier. Also it was found that l-valine-acyclovir inhibits the uptake of cephalexin, a substrate for the oligopeptide transporter. Stability of the esters in either the mucosal or serosal bathing solution is more than 90% after completion of the transport study. However, after transport, the receiver solution contained approximately 90% of acyclovir. Based on these findings it was concluded that absorption of thel-valine ester of acyclovir occurs as a result of uptake by the oligopeptide transporter at the apical cell membrane followed by intracellular hydrolysis of the ester and efflux of acyclovir.

Footnotes

  • Send reprint requests to: Dr. Chao-Pin Lee, Department of Drug Delivery UP1230, SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, P.O. Box 5089, Collegeville, PA 19426-0989.

  • ↵1 Current address: Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.

  • Abbreviations:
    GI
    gastrointestinal
    Gly-Sar
    L-glycyl-sarcosine
    L-val-acv
    L-val-acyclovir
    m
    mucosal
    S
    serosal
    cbz
    benzyl carbamate
    [H]NMR
    proton nuclear magnetic resonance
    DMEM
    Dulbecco’s Modified Eagle medium
    NEAA
    non-essential amino acid solution
    • Received January 28, 1998.
    • Accepted May 12, 1998.
  • 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
Vol. 286, Issue 3
1 Sep 1998
  • Table of Contents
  • 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.
Transport of l-Valine-Acyclovir Via the Oligopeptide Transporter In The Human Intestinal Cell Line, Caco-2
(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

Transport of l-Valine-Acyclovir Via the Oligopeptide Transporter In The Human Intestinal Cell Line, Caco-2

Remco L. A. de Vrueh, Philip L. Smith and Chao-Pin Lee
Journal of Pharmacology and Experimental Therapeutics September 1, 1998, 286 (3) 1166-1170;

Citation Manager Formats

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

Transport of l-Valine-Acyclovir Via the Oligopeptide Transporter In The Human Intestinal Cell Line, Caco-2

Remco L. A. de Vrueh, Philip L. Smith and Chao-Pin Lee
Journal of Pharmacology and Experimental Therapeutics September 1, 1998, 286 (3) 1166-1170;
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
  • Toxicity, Biological Activity, and Pharmacokinetics of TXU (Anti-CD7)-Pokeweed Antiviral Protein in Chimpanzees and Adult Patients Infected with Human Immunodeficiency Virus
  • Evidence That Melanocortin 4 Receptor Mediates Hemorrhagic Shock Reversal Caused by Melanocortin Peptides
Show more Article

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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics