Skip to main content

Main menu

  • Home
  • Content
    • Current Issue
    • Past Issues
    • Accepted Articles
    • Email Alerts
    • RSS
    • Terms of Use
  • About PDA JPST
    • JPST Editors and Editorial Board
    • About/Vision/Mission
    • Paper of the Year
  • Author & Reviewer Resources
    • Author Resources / Submit
    • Reviewer Resources
  • JPST Access and Subscriptions
    • PDA Members
    • Institutional Subscriptions
    • Nonmember Access
  • Support
    • Join PDA
    • Contact
    • Feedback
    • Advertising
    • CiteTrack
  • .
    • Visit PDA
    • PDA Letter
    • Technical Reports
    • news uPDATe
    • Bookstore

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
PDA Journal of Pharmaceutical Science and Technology
  • .
    • Visit PDA
    • PDA Letter
    • Technical Reports
    • news uPDATe
    • Bookstore
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
PDA Journal of Pharmaceutical Science and Technology

Advanced Search

  • Home
  • Content
    • Current Issue
    • Past Issues
    • Accepted Articles
    • Email Alerts
    • RSS
    • Terms of Use
  • About PDA JPST
    • JPST Editors and Editorial Board
    • About/Vision/Mission
    • Paper of the Year
  • Author & Reviewer Resources
    • Author Resources / Submit
    • Reviewer Resources
  • JPST Access and Subscriptions
    • PDA Members
    • Institutional Subscriptions
    • Nonmember Access
  • Support
    • Join PDA
    • Contact
    • Feedback
    • Advertising
    • CiteTrack
  • Follow pda on Twitter
  • Visit PDA on LinkedIn
  • Visit pda on Facebook
Research ArticleRESEARCH ARTICLE

The Effect of Lipoprotein-Associated Cyclosporine on Drug Metabolism and Toxicity in Rats

Taekrho Kim, Shirley K. Lu and Lane J. Brunner
PDA Journal of Pharmaceutical Science and Technology November 2003, 57 (6) 410-424;
Taekrho Kim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shirley K. Lu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lane J. Brunner
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: lane.brunner@mail.utexas.edu
  • Article
  • References
  • Info & Metrics
  • PDF
Loading

Abstract

Purpose: The objective of the study was to examine the effect of lipoprotein-associated cyclosporine on hepatic metabolism, hepatic lipoprotein receptors, and renal toxicity in comparison to the current commercially available cyclosporine (CSA) product. Methods: Rats within the same group were given one of the following treatments: 10 mg/kg of CSA, plasma-CSA, very low-density lipoprotein (VLDL)-CSA, low-density lipoprotein (LDL)-CSA, LDL, high-density lipoprotein (HDL)-CSA, 1 mL/kg of vehicle, or saline intravenously for 14 days. Urine and blood samples were evaluated for renal function. Hepatic microsomes were prepared for immunoblotting and in vitro catalytic assays of CYP activity. Reverse transcription polymerase chain reaction (RT-PCR) was used to examine genetic regulation. Results: (1) There were no statistical differences in cholesterol levels in lipoprotein-associated CSA groups as compared with vehicle controls. (2) A significant decrease in creatinine clearance was seen in the plasma-CSA treated group (56%; P < 0.05). (3) No suppressions of CYP3A protein, activity or mRNA were found in the VLDL-CSA treated group. (4) CYP3A mRNA was suppressed to a greater degree in the LDL- and HDL-CSA treated groups as compared with the suppression caused by CSA alone. (5) A significant suppression of hepatic low-density lipoprotein receptor (LDL-R) mRNA levels was found in the LDL-CSA (50%; P = 0.0333) and plasma-CSA (40%; P = 0.1138), which was not attributed to LDL alone. (6) Significant suppression of scavenger-receptors class B type I (SR-BI) mRNA levels was found in the plasma-CSA group, although no significant differences in SRBI protein levels were seen between groups. Conclusions: Specific lipoprotein-CSA complexes appear to alter metabolic responses differently in comparison to CSA alone, indicating that the metabolism of CSA is dependent on the in vivo disposition of lipoprotein-CSA. Furthermore, LDL-R is one regulatory factor responsible for altering CSA metabolism as a result of an increase in uptake of CSA into hepatocytes.

Footnotes

  • ↵1 This work was supported, in part, by a grant from the Parenteral Drug Association and the William Orr Dingwall Foundation.

  • Copyright © Parenteral Drug Association. All rights reserved.

PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.  

If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing. 

Full issue PDFs are for PDA members only.

Note to pda.org users

The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.

Log in using your username and password

Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.

patientACCESS

patientACCESS - Patients desiring access to articles

Full issue PDFs are for PDA members only. You can join PDA at www.pda.org. 

PreviousNext
Back to top

In This Issue

PDA Journal of Pharmaceutical Science and Technology
Vol. 57, Issue 6
November/December 2003
  • Table of Contents
  • Index by Author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on PDA Journal of Pharmaceutical Science and Technology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
The Effect of Lipoprotein-Associated Cyclosporine on Drug Metabolism and Toxicity in Rats
(Your Name) has sent you a message from PDA Journal of Pharmaceutical Science and Technology
(Your Name) thought you would like to see the PDA Journal of Pharmaceutical Science and Technology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
1 + 0 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
The Effect of Lipoprotein-Associated Cyclosporine on Drug Metabolism and Toxicity in Rats
Taekrho Kim, Shirley K. Lu, Lane J. Brunner
PDA Journal of Pharmaceutical Science and Technology Nov 2003, 57 (6) 410-424;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
The Effect of Lipoprotein-Associated Cyclosporine on Drug Metabolism and Toxicity in Rats
Taekrho Kim, Shirley K. Lu, Lane J. Brunner
PDA Journal of Pharmaceutical Science and Technology Nov 2003, 57 (6) 410-424;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • References
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Monitoring of Mannitol Phase Behavior during Freeze-Drying Using Non-Invasive Raman Spectroscopy
  • Long-Term Stabilization of a New Freeze-Dried and Albumin-Free Formulation of Recombinant Human Interferon Alpha 2b
  • Pharmaceutical Development of an Intravenous Dosage Form of Diacetylmorphine Hydrochloride
Show more Research Article

Similar Articles

Readers

  • About
  • Table of Content Alerts/Other Alerts
  • Subscriptions
  • Terms of Use
  • Contact Editors

Author/Reviewer Information

  • Author Resources
  • Submit Manuscript
  • Reviewers
  • Contact Editors

Parenteral Drug Association, Inc.

  • About
  • Advertising/Sponsorships
  • Events
  • PDA Bookstore
  • Press Releases

© 2023 PDA Journal of Pharmaceutical Science and Technology ISSN: 1079-7440

Powered by HighWire