Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Effect of Albumin on the Biliary Clearance of Compounds in Sandwich-Cultured Rat Hepatocytes

Kristina K. Wolf, Kenneth R. Brouwer, Gary M. Pollack and Kim L. R. Brouwer
Drug Metabolism and Disposition October 2008, 36 (10) 2086-2092; DOI: https://doi.org/10.1124/dmd.108.020842
Kristina K. Wolf
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenneth R. Brouwer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gary M. Pollack
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kim L. R. Brouwer
  • 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 purpose of the present study was to evaluate the effects of bovine serum albumin (BSA) and essentially fatty acid-free BSA (BSA-FAF) on the biliary clearance of compounds in sandwich-cultured rat hepatocytes. Unbound fraction, biliary excretion index (BEI), and unbound intrinsic biliary clearance (intrinsic Math) were determined for digoxin, pravastatin, and taurocholate in the absence or presence of BSA or BSA-FAF. BSA had little effect on the BEI or intrinsic Math of these compounds. Surprisingly, BSA-FAF decreased both BEI and intrinsic Math for digoxin and pravastatin, which represent low and moderately bound compounds, respectively. The BEI and intrinsic Math of taurocholate, a highly bound compound, were not altered significantly by BSA-FAF. Neither BSA nor BSA-FAF had a discernable effect on the bile canalicular networks based on carboxydichlorofluorescein retention. Neither the addition of physiological concentrations of calcium nor the addition of fatty acids to BSA-FAF was able to restore the BEI or intrinsic Math of the model compounds to similar values in the absence or presence of BSA. Careful consideration is warranted when selecting the type of BSA for addition to in vitro systems such as sandwich-cultured rat hepatocytes.

Footnotes

  • This work was supported by National Institutes of Health Grant GM41935. K.K.W. was supported by a postdoctoral fellowship from GlaxoSmithKline Inc. Data were presented at the American Association of Pharmaceutical Scientists Annual Meeting and Exposition in San Diego, CA, November 2007.

  • K.L.R.B. is cofounder and Chair of the Scientific Advisory Board for Qualyst, Inc., which has exclusively licensed the sandwich-cultured hepatocyte technology for quantification of biliary excretion (B-CLEAR).

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.108.020842.

  • ABBREVIATIONS: BSA, bovine serum albumin; UGT, UDP-glucuronosyltransferase; BSA-FAF, essentially fatty acid-free bovine serum albumin; BEI, biliary excretion index; fu, unbound fraction; DMEM, Dulbecco's modified Eagle's medium; MEM, minimal essential medium; CDFDA, 5 (and 6)-carboxy-2′,7′-dichlorofluorescein diacetate; HBSS, Hanks' balanced salt solution; BCA, bicinchoninic acid; LC/MS/MS, liquid chromatography with detection by tandem mass spectrometry; CDF, 5 (and 6)-carboxy-2′,7′-dichlorofluorescein; intrinsic Math, unbound intrinsic biliary clearance; Ntcp, sodium-taurocholate cotransporting polypeptide; Oatp/OATP, organic anion-transporting polypeptide.

    • Received February 6, 2008.
    • Accepted July 22, 2008.
  • 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: 36 (10)
Drug Metabolism and Disposition
Vol. 36, Issue 10
1 Oct 2008
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front 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.
Effect of Albumin on the Biliary Clearance of Compounds in Sandwich-Cultured Rat Hepatocytes
(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

Effect of Albumin on the Biliary Clearance of Compounds in Sandwich-Cultured Rat Hepatocytes

Kristina K. Wolf, Kenneth R. Brouwer, Gary M. Pollack and Kim L. R. Brouwer
Drug Metabolism and Disposition October 1, 2008, 36 (10) 2086-2092; DOI: https://doi.org/10.1124/dmd.108.020842

Citation Manager Formats

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

Effect of Albumin on the Biliary Clearance of Compounds in Sandwich-Cultured Rat Hepatocytes

Kristina K. Wolf, Kenneth R. Brouwer, Gary M. Pollack and Kim L. R. Brouwer
Drug Metabolism and Disposition October 1, 2008, 36 (10) 2086-2092; DOI: https://doi.org/10.1124/dmd.108.020842
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike 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

  • BSEP Function in Suspension Hepatocytes
  • Candesartan glucuronide serves as a CYP2C8 inhibitor
  • Role of AADAC on eslicarbazepine acetate hydrolysis
Show more Articles

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics