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
Abstract

Stereochemical composition of propranolol metabolites in the dog using stable isotope-labeled pseudoracemates.

T Walle, M J Wilson, U K Walle and S A Bai
Drug Metabolism and Disposition November 1983, 11 (6) 544-549;
T Walle
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M J Wilson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
U K Walle
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S A Bai
  • 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

Previous studies have demonstrated a larger oral bioavailability of (+)- as compared to (-)-propranolol in the dog. The objective of the present study was to examine how this difference is reflected in the metabolism in the drug. The stereochemical composition of propranolol and its metabolites was, therefore, determined in the urine of four dogs after single 160-mg oral doses of stable isotope-labeled pseudoracemates of propranolol. All major metabolites, accounting for 84% of the dose excreted in urine, were isolated by solvent extraction or HPLC, glucuronic acid conjugates after enzymatic hydrolysis, and analyzed by GC/MS after chemical derivatization. Of the three primary metabolic pathways, glucuronidation of the parent drug, about 16% of the dose recovered in urine, was highly selective for (-)-propranolol, (-)/(+)-enantiomer ratio 3.5. In contrast, all of the side-chain oxidation metabolites, about 30% of the dose, were mainly derived from (+)-propranolol, (-)/(+)-enantiomer ratio ranging from 0.35 to 0.74. Ring oxidation, involved in the metabolism of the remainder of the dose studied, about 38%, was, however, also found to be selective for (-)-propranolol, with the greatest selectivity observed in 4'-hydroxypropranolol, (-/(+)-enantiomer ratio 1.49. There was an excellent mass balance for the enantiomers of the metabolites studied, i.e. the total (-)/(+)-enantiomer ratio was close to unity. The higher oral bioavailability of (+)-propranolol in the dog, well reflected in the stereochemical composition of unchanged propranolol in urine, is suggested to be due to stereoselective presystemic hepatic removal of (-)-propranolol by glucuronidation and ring oxidation.

 

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
Vol. 11, Issue 6
1 Nov 1983
  • Table of Contents
  • Index by author
  • Back Matter (PDF)
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.
Stereochemical composition of propranolol metabolites in the dog using stable isotope-labeled pseudoracemates.
(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
Abstract

Stereochemical composition of propranolol metabolites in the dog using stable isotope-labeled pseudoracemates.

T Walle, M J Wilson, U K Walle and S A Bai
Drug Metabolism and Disposition November 1, 1983, 11 (6) 544-549;

Citation Manager Formats

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

Share
Abstract

Stereochemical composition of propranolol metabolites in the dog using stable isotope-labeled pseudoracemates.

T Walle, M J Wilson, U K Walle and S A Bai
Drug Metabolism and Disposition November 1, 1983, 11 (6) 544-549;
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
  • 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 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