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

Verapamil Metabolite Exposure in Older and Younger Men during Steady-State Oral Verapamil Administration

Darrell R. Abernethy, Irving W. Wainer and Ana Isabel Anacleto
Drug Metabolism and Disposition July 2000, 28 (7) 760-765;
Darrell R. Abernethy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Irving W. Wainer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ana Isabel Anacleto
  • 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

To determine the effect of age on exposure to the circulating major verapamil metabolites norverapamil, N-dealkylverapamil (D-617), and N-dealkylnorverapamil (D-620), plasma concentrations of verapamil and the three metabolites were determined during the last dose interval of a 14-day administration period of 240 mg of sustained release verapamil once daily in 11 older (aged 65–75 years) and 8 younger (20–28 years) healthy male volunteers. Area under the plasma concentration time curve (AUC) was greater for verapamil (mean ± S.D.) (2815 ± 733 older versus 1639 ± 466 ng/ml·h−1 young;P < .0007) and norverapamil (2927 ± 655 versus 2143 ± 471 ng/ml·h−1; P< .007); however, it was not significantly different for D-617 [2386 ± 772 versus 1894 ± 418 ng/ml·h−1; not significantly different (NS)] andN-dealkylnorverapamil (897 ± 366 versus 757 ± 104 ng/ml·h−1; NS) in older as compared with young subjects. These data indicate that impaired verapamil oral clearance previously described in older men does not result in decreased exposure to the formed major metabolites, rather there is increased exposure to norverapamil and the same or a trend toward greater exposure to D-617 as well. This suggests that in addition to the impaired clearance mechanisms for verapamil, which are thought to be primarily mediated by CYP3A, biotransformation processes distal to the formation of norverapamil and D-617 are impaired as well.

Footnotes

  • Send reprint requests to: Darrell R. Abernethy, M.D., Ph.D., Clinical Director, National Institute on Aging, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825. E-mail: abernethyd{at}grc.nia.nih.gov

  • This work was supported in part by National Institutes of Health Grants AG-08226 and GM-08386.

  • Abbreviations used are::
    D-617
    N-dealkylverapamil
    D-620
    N-dealkylnorverapamil
    AUC
    area under the plasma concentration time curve
    PR-22 (2-[4-hydroxy-3-methoxyphenyl]-8-[3,4-dimethoxyphenyl]-6-methyl-2-isopropyl-6-azaoctanitrile)
    PR-25 ([3,4-dimethoxyphenyl]-acetic acid)
    • Received November 22, 1999.
    • Accepted March 13, 2000.
  • 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: 28 (7)
Drug Metabolism and Disposition
Vol. 28, Issue 7
1 Jul 2000
  • 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.
Verapamil Metabolite Exposure in Older and Younger Men during Steady-State Oral Verapamil Administration
(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

Verapamil Metabolite Exposure in Older and Younger Men during Steady-State Oral Verapamil Administration

Darrell R. Abernethy, Irving W. Wainer and Ana Isabel Anacleto
Drug Metabolism and Disposition July 1, 2000, 28 (7) 760-765;

Citation Manager Formats

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

Share
Research ArticleArticle

Verapamil Metabolite Exposure in Older and Younger Men during Steady-State Oral Verapamil Administration

Darrell R. Abernethy, Irving W. Wainer and Ana Isabel Anacleto
Drug Metabolism and Disposition July 1, 2000, 28 (7) 760-765;
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

  • Determination of Acyl-, O-, and N-Glucuronide
  • TMDD Affects PK of IL-10 Fc-fusion Proteins
  • Uptake as the RDS in Pevonedistat Hepatic Clearance
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