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

AN EVALUATION METHOD FOR NONLINEAR LOCAL DISPOSITION IN RAT LIVER AND KIDNEY

Takako Kato, Kiyoshi Yamaoka and Yoshinobu Takakura
Drug Metabolism and Disposition February 2004, 32 (2) 230-234; DOI: https://doi.org/10.1124/dmd.32.2.230
Takako Kato
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kiyoshi Yamaoka
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoshinobu Takakura
  • 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

A two-sampling sites method was developed to separately estimate the nonlinear local disposition in the liver and kidney by sampling blood simultaneously from the hepatic vein and an artery after intravenous administration. Using this method, it was attempted to predict the renal elimination from the systemic and hepatic elimination. Etoposide, a substrate of both P-glycoprotein and CYP3A, was used as a model drug. The blood samples from the hepatic vein and an artery were simultaneously taken from a rat after intravenous administration of etoposide at a dose of 20 or 80 mg/kg. At a dose of 20 mg/kg, the total clearance (CL), hepatic clearance (CLH), and renal clearance (CLR = CL - CLH), which were almost constant, were 2.82 ± 0.24, 0.742 ± 0.214, and 2.09 ± 0.34 l/h/kg, respectively. At a dose of 80 mg/kg, CL and CLR considerably decreased with an increase in plasma concentration, whereas CLH slightly decreased. By means of the two-sampling sites method, we estimated the local drug disposition in the liver and kidney. The present local pharmacokinetic method would be applicable to assess the local disposition of other drugs that are mainly metabolized in these organs.

Footnotes

  • ↵1 Abbreviations used are: P-gp, P-glycoprotein; HPLC, high-performance liquid chromatography; RB, whole blood to plasma partition ratio; CL, clearance; MRT, mean residence time; GI, gastrointestinal.

    • Received April 30, 2003.
    • Accepted October 17, 2003.
  • 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: 32 (2)
Drug Metabolism and Disposition
Vol. 32, Issue 2
1 Feb 2004
  • 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.
AN EVALUATION METHOD FOR NONLINEAR LOCAL DISPOSITION IN RAT LIVER AND KIDNEY
(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

AN EVALUATION METHOD FOR NONLINEAR LOCAL DISPOSITION IN RAT LIVER AND KIDNEY

Takako Kato, Kiyoshi Yamaoka and Yoshinobu Takakura
Drug Metabolism and Disposition February 1, 2004, 32 (2) 230-234; DOI: https://doi.org/10.1124/dmd.32.2.230

Citation Manager Formats

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

Share
Research ArticleArticle

AN EVALUATION METHOD FOR NONLINEAR LOCAL DISPOSITION IN RAT LIVER AND KIDNEY

Takako Kato, Kiyoshi Yamaoka and Yoshinobu Takakura
Drug Metabolism and Disposition February 1, 2004, 32 (2) 230-234; DOI: https://doi.org/10.1124/dmd.32.2.230
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results and Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Metabolic enzymes in nintedanib metabolism
  • Mechanism of AO Inactivation by Hydralazine
  • Warfarin PBPK modeling with target binding
Show more Articles

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