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

ATP-DEPENDENT TRANSPORT OF ROSUVASTATIN IN MEMBRANE VESICLES EXPRESSING BREAST CANCER RESISTANCE PROTEIN

Liyue Huang, Yi Wang and Scott Grimm
Drug Metabolism and Disposition May 2006, 34 (5) 738-742; DOI: https://doi.org/10.1124/dmd.105.007534
Liyue Huang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yi Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott Grimm
  • 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

MDR1/ABCB1, MRP2/ABCC2, and breast cancer resistance protein (BCRP)/ABCG2 are expressed in the liver and intestine and contribute to the disposition of many drugs. Rosuvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor for the treatment of patients with dyslipidemia, is primarily excreted via bile as unchanged drug. The present study was designed to determine whether rosuvastatin is transported by MDR1, MRP2, and BCRP. The apparent permeability value for rosuvastatin across MDR1-Madin-Darby canine kidney cells was low (∼8 nm/s), and no directional transport was observed. Rosuvastatin uptake into control Sf9 membranes and membranes expressing MRP2 was similar in the presence or absence of GSH. In contrast, ATP dramatically stimulated rosuvastatin uptake into membranes expressing BCRP, but not control membranes. Rosuvastatin transport occurred into an osmotically sensitive space and was saturable. An Eadie-Hofstee analysis suggested that there were two transport sites in BCRP, with an apparent Km of 10.8 μM for the high affinity site and 307 μM for the low affinity site. These data demonstrate that rosuvastatin is transported efficiently by BCRP and suggest that BCRP plays a significant role in the disposition of rosuvastatin.

Footnotes

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

  • doi:10.1124/dmd.105.007534.

  • ABBREVIATIONS: ABC, ATP-binding cassette transporter; BCRP, breast cancer resistance protein; E217G, estradiol-17β-d-glucuronide; GSH, glutathione; MDR1, multidrug resistance protein 1; MDR1-MDCK, Madin-Darby canine kidney cells transfected with the human MDR1 gene; MRP2, multidrug resistance protein 2; MXR, mitoxantrone resistance protein; Papp, apparent permeability; Pgp, P-glycoprotein; OATP, organic anion-transporting polypeptide; GF120918, N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide; CTRL, control; A→B apical to basolateral; B→A, basolateral to apical.

  • ↵1 Current affiliation: Amgen, Cambridge, Massachusetts.

    • Received September 20, 2005.
    • Accepted December 28, 2005.
  • 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: 34 (5)
Drug Metabolism and Disposition
Vol. 34, Issue 5
1 May 2006
  • 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.
ATP-DEPENDENT TRANSPORT OF ROSUVASTATIN IN MEMBRANE VESICLES EXPRESSING BREAST CANCER RESISTANCE PROTEIN
(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

ATP-DEPENDENT TRANSPORT OF ROSUVASTATIN IN MEMBRANE VESICLES EXPRESSING BREAST CANCER RESISTANCE PROTEIN

Liyue Huang, Yi Wang and Scott Grimm
Drug Metabolism and Disposition May 1, 2006, 34 (5) 738-742; DOI: https://doi.org/10.1124/dmd.105.007534

Citation Manager Formats

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

ATP-DEPENDENT TRANSPORT OF ROSUVASTATIN IN MEMBRANE VESICLES EXPRESSING BREAST CANCER RESISTANCE PROTEIN

Liyue Huang, Yi Wang and Scott Grimm
Drug Metabolism and Disposition May 1, 2006, 34 (5) 738-742; DOI: https://doi.org/10.1124/dmd.105.007534
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

  • Deoxycholate Oxidation is Predictive of CYP3A Activity
  • Retroconversion of PQ and its N-oxide metabolites
  • HNF4A-AS1 regulates CYPs via histone modifications
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