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
Abstract

Pharmacokinetics and tissue disposition of a chimeric oligodeoxynucleoside phosphorothioate in rats after intravenous administration.

R Zhang, R P Iyer, D Yu, W Tan, X Zhang, Z Lu, H Zhao and S Agrawal
Journal of Pharmacology and Experimental Therapeutics August 1996, 278 (2) 971-979;
R Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R P Iyer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D Yu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
W Tan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
X Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Z Lu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
H Zhao
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S Agrawal
  • 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

Antisense oligonucleotides represent a novel therapeutic principle for designing drugs against various diseases. Oligonucleotides can be chemically modified to improve their pharmacokinetics and in vivo stability, and it is important to understand the effect of these modifications. In the present study, the pharmacokinetics of a 25-mer phosphorothioate oligonucleotide containing four contiguous, internucleotide, methylphosphonate linkages at the 3'- and 5'-ends (chimeric oligonucleotide) were determined in rats after i.v. administration of the 35S-labeled oligonucleotide at a dose of 30 mg/kg. Plasma disappearance of the oligonucleotide could be described by a two-compartment model, with half-lives of 0.38 and 52.9 hr. The intact chimeric oligonucleotide was detected in plasma up to 6 hr after dosing. Urinary excretion represented the major elimination pathway, with approximately 21% of the administered dose being excreted within 24 hr and 35% being excreted over a 240-hr period after dosing. The majority of the radioactivity in urine was associated with the intact oligonucleotide within 6 hr after dosing and with increasing degradation products thereafter. Fecal excretion was a minor elimination pathway. The oligonucleotide was widely distributed in tissues, with the majority of the radioactivity in most tissues being intact up to 48 hr after dosing. Compared with oligodeoxynucleotide phosphorothioates, the chimeric oligonucleotide was significantly more stable in vivo. The presence of intact oligonucleotide in plasma and tissues even 12 hr after dosing is a significant advantage over an "all"-phosphorothioate analog. Thus, the chimeric oligonucleotide could provide a longer duration of action as an antisense agent after its administration.

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. 278, Issue 2
1 Aug 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.
Pharmacokinetics and tissue disposition of a chimeric oligodeoxynucleoside phosphorothioate in rats after intravenous administration.
(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

Pharmacokinetics and tissue disposition of a chimeric oligodeoxynucleoside phosphorothioate in rats after intravenous administration.

R Zhang, R P Iyer, D Yu, W Tan, X Zhang, Z Lu, H Zhao and S Agrawal
Journal of Pharmacology and Experimental Therapeutics August 1, 1996, 278 (2) 971-979;

Citation Manager Formats

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

Pharmacokinetics and tissue disposition of a chimeric oligodeoxynucleoside phosphorothioate in rats after intravenous administration.

R Zhang, R P Iyer, D Yu, W Tan, X Zhang, Z Lu, H Zhao and S Agrawal
Journal of Pharmacology and Experimental Therapeutics August 1, 1996, 278 (2) 971-979;
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
  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics