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

2′-β-Fluoro-2′,3′-dideoxyadenosine, Lodenosine, in Rhesus Monkeys: Plasma and Cerebrospinal Fluid Pharmacokinetics and Urinary Disposition

Jeri S. Roth, Cynthia M. McCully, Frank M. Balis, David G. Poplack and James A. Kelley
Drug Metabolism and Disposition October 1999, 27 (10) 1128-1132;
Jeri S. Roth
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cynthia M. McCully
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frank M. Balis
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David G. Poplack
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James A. Kelley
  • 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

2′-β-Fluoro-2′,3′-dideoxyadenosine (F-ddA, lodenosine) is a nucleoside analog that was rationally designed as a more chemically and enzymatically stable anti-AIDS drug than its parent compound 2′,3′-dideoxyadenosine or didanosine. Plasma and cerebrospinal fluid (CSF) pharmacokinetics of this compound and its major metabolite, 2′-β-fluoro-2′,3′-dideoxyinosine (F-ddI), were studied in three rhesus monkeys after a single 20 mg/kg dose administered as an i.v. push. F-ddA exhibited a mean residence time of 0.17 h in plasma and its plasma concentration time profile appeared to be biexponential. The majority of plasma exposure was from F-ddI, with a mean parent drug area under the curve (AUC) to metabolite AUC ratio of 0.16. CSF levels were low, with a mean CSF AUC to plasma AUC ratio of 0.068, with approximately one-quarter of this exposure in CSF due to unchanged drug. Urinary excretion accounted for half of the drug administered with the majority recovered as the metabolite, F-ddI. In a separate experiment, one monkey received a 20 mg/kg i.v. dose of F-ddI. The total dideoxynucleoside plasma exposure was greater than it was after administration of F-ddA; however, the CSF AUC to plasma AUC ratio was a factor of 4 lower (0.017). Thus, F-ddA central nervous system penetration is at least comparable to that of didanosine, indicating that this experimental drug has potential as an addition to currently approved AIDS therapies.

Footnotes

  • Send reprint requests to: Jeri S. Roth, Laboratory of Medicinal Chemistry, Bldg. 37, Room 5C-02, 37 Convent Drive, National Institutes of Health, Bethesda, MD 20892. E-mail:rothj{at}dc37a.nci.nih.gov

  • ↵1 Some of the data in this paper were originally presented at the 1992 Pittsburgh Conference & Exposition on Analytical Chemistry and Applied Spectroscopy, March 11, 1992, New Orleans, LA, and at the Sixteenth International Symposium on Column Liquid Chromatography, June 16, 1992, Baltimore, MD.

  • Abbreviations used are::
    F-ddA
    2′-β-fluoro-2′,3′-dideoxyadenosine
    ddA
    2′,3′-dideoxyadenosine
    ddI
    2′,3′-dideoxyinosine
    ADA
    adenosine deaminase
    CNS
    central nervous system
    ddG
    2′,3′-dideoxyguanosine
    CSF
    cerebrospinal fluid
    F-ddI
    2′-β-fluoro-2′,3′-dideoxyinosine
    AUC
    area under the curve
    MRT
    mean residence time
    PNP
    purine nucleoside phosphorylase
    DMSO
    dimethyl sulfoxide
    • Received February 17, 1999.
    • Accepted June 16, 1999.
  • U.S. Government
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: 27 (10)
Drug Metabolism and Disposition
Vol. 27, Issue 10
1 Oct 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 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.
2′-β-Fluoro-2′,3′-dideoxyadenosine, Lodenosine, in Rhesus Monkeys: Plasma and Cerebrospinal Fluid Pharmacokinetics and Urinary Disposition
(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

2′-β-Fluoro-2′,3′-dideoxyadenosine, Lodenosine, in Rhesus Monkeys: Plasma and Cerebrospinal Fluid Pharmacokinetics and Urinary Disposition

Jeri S. Roth, Cynthia M. McCully, Frank M. Balis, David G. Poplack and James A. Kelley
Drug Metabolism and Disposition October 1, 1999, 27 (10) 1128-1132;

Citation Manager Formats

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

Share
Research ArticleArticle

2′-β-Fluoro-2′,3′-dideoxyadenosine, Lodenosine, in Rhesus Monkeys: Plasma and Cerebrospinal Fluid Pharmacokinetics and Urinary Disposition

Jeri S. Roth, Cynthia M. McCully, Frank M. Balis, David G. Poplack and James A. Kelley
Drug Metabolism and Disposition October 1, 1999, 27 (10) 1128-1132;
del.icio.us logo Digg logo Reddit logo Twitter 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

  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
  • Biotransformation of Trastuzumab and Pertuzumab
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 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