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

Blood Thiols Following Amifostine and Mesna Infusions, a Pediatric Oncology Group Study

Abdul-Kader Souid, Robert C. Fahey, Mehmet K. Aktas, Omer A. Sayin, Sara Karjoo, Gerald L. Newton, Peter D. Sadowitz, Ronald L. Dubowy and Mark L. Bernstein
Drug Metabolism and Disposition November 2001, 29 (11) 1460-1466;
Abdul-Kader Souid
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert C. Fahey
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mehmet K. Aktas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Omer A. Sayin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sara Karjoo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gerald L. Newton
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter D. Sadowitz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ronald L. Dubowy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark L. Bernstein
  • 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 Pediatric Oncology Group study for metastatic Ewing's sarcoma used amifostine and mesna with the alkylating agents. To determine the fate of combined drug thiols, we measured thiol levels in plasma, red blood cells (RBC), and peripheral blood mononuclear cells (PBMC) of four patients. We also conducted analogous measurements on two patients who received mesna alone and a volunteer's blood following in vitro treatment. Thiols were labeled with monobromobimane, separated on high-pressure liquid chromatography, and detected by fluorescence. Incubation of a volunteer's blood with mesna, WR-1065, or both revealed that cellular uptake of total reducible drug was ∼10% of plasma level for mesna but ∼60% for WR-1065. Cellular drugs were mainly the thiol form, whereas half of the plasma drugs were disulfides. Combined incubation with both thiols did not change the extent or form of uptake. WR-1065 and mesna prevented glutathione depletion by 4-hydroperoxycyclophosphamide. Results from patients were similar. WR-1065 and mesna appeared in the cells by the end of the drug infusions, although WR-1065 uptake was more efficient than mesna. The concentration-time profiles of mesna in RBC paralleled those in plasma. Amifostine administration during mesna infusion caused transient increase in mesna levels. Both agents increased blood cysteine and decreased total reducible cysteine. Mesna alone and mesna plus amifostine prevented cellular glutathione depletion. In conclusion, mesna is imported by RBC and PBMC, but less efficiently than WR-1065. When present at equal levels, these thiols do not influence each other's uptake. Adequate dosing of either drug is necessary for protecting the cells from toxic effects of alkylating agents.

Footnotes

  • This work was supported by the Children's Health Fund, Alfred T. Murphy's Fund, and U.S. Bioscience to the Pediatric Oncology Group.

  • Abbreviations used are::
    RBC
    red blood cells
    PBMC
    peripheral blood mononuclear cells
    mBBr
    monobromobimane
    Cys-SH
    cysteine
    HPLC
    high-performance liquid chromatography
    AcCN
    acetonitrile
    MSA
    methanesulfonic acid
    DTT
    dithiothreitol
    PBS
    phosphate-buffered saline
    RT
    room temperature
    LMW
    low-molecular weight
    GSH
    glutathione
    GSSG
    oxidized glutathione
    WR-SH
    WR-1065
    M-SH
    mesna
    4-OOH-CP
    4-hydroperoxycyclophosphamide
    DMSO
    dimethyl sulfoxide
    • Received May 3, 2001.
    • Accepted July 26, 2001.
  • 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: 29 (11)
Drug Metabolism and Disposition
Vol. 29, Issue 11
1 Nov 2001
  • 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.
Blood Thiols Following Amifostine and Mesna Infusions, a Pediatric Oncology Group Study
(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

Blood Thiols Following Amifostine and Mesna Infusions, a Pediatric Oncology Group Study

Abdul-Kader Souid, Robert C. Fahey, Mehmet K. Aktas, Omer A. Sayin, Sara Karjoo, Gerald L. Newton, Peter D. Sadowitz, Ronald L. Dubowy and Mark L. Bernstein
Drug Metabolism and Disposition November 1, 2001, 29 (11) 1460-1466;

Citation Manager Formats

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

Share
Research ArticleArticle

Blood Thiols Following Amifostine and Mesna Infusions, a Pediatric Oncology Group Study

Abdul-Kader Souid, Robert C. Fahey, Mehmet K. Aktas, Omer A. Sayin, Sara Karjoo, Gerald L. Newton, Peter D. Sadowitz, Ronald L. Dubowy and Mark L. Bernstein
Drug Metabolism and Disposition November 1, 2001, 29 (11) 1460-1466;
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
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Role of Human MSRA on Sulindac Activation
  • Determination of Acyl-, O-, and N-Glucuronide
  • TMDD Affects PK of IL-10 Fc-fusion Proteins
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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics