Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    Oral and inhaled corticosteroids: Differences in P-glycoprotein (ABCB1) mediated efflux

    Access Status
    Fulltext not available
    Authors
    Crowe, Andrew
    Tan, A.
    Date
    2012
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Crowe, Andrew and Tan, Ai. 2012. Oral and inhaled corticosteroids: Differences in P-glycoprotein (ABCB1) mediated efflux. Toxicology and Applied Pharmacology. 260 (3): pp. 294-302.
    Source Title
    Toxicology and Applied Pharmacology
    DOI
    10.1016/j.taap.2012.03.008
    ISSN
    0041-008X
    School
    School of Pharmacy
    URI
    http://hdl.handle.net/20.500.11937/21050
    Collection
    • Curtin Research Publications
    Abstract

    There is concern that P-glycoprotein mediated efflux contributes to steroid resistance. Therefore, this study examined bidirectional corticosteroid transport and induction capabilities for P-glycoprotein (P-gp) to understand which of the systemic and inhaled corticosteroids interacted with P-gp to the greatest extent. Hydrocortisone, prednisolone, prednisone, methylprednisolone, and dexamethasone represented systemically active drugs, while fluticasone propionate, beclomethasone dipropionate, ciclesonide and budesonide represented inhaled corticosteroids. Aldosterone and fludrocortisone represented mineralocorticoids. All drugs were detected using individually optimised HPLC protocols. Transport studies were conducted through Caco-2 monolayers. Hydrocortisone and aldosterone had efflux ratios below 1.5, while prednisone showed a P-gp mediated efflux ratio of only 1.8 compared to its active drug, prednisolone, with an efflux ratio of 4.5. Dexamethasone and beclomethasone had efflux ratios of 2.1 and 3.3 respectively, while this increased to 5.1 for methylprednisolone. Fluticasone showed an efflux ratio of 2.3. Protein expression studies suggested that all of the inhaled corticosteroids were able to induce P-gp expression, from 1.6 to 2 times control levels. Most of the systemic corticosteroids had higher passive permeability (>20×10−6 cm/s) compared to the inhaled corticosteroids (>5×10−6 cm/s), except for budesonide, with permeability similar to the systemic corticosteroids. Inhaled corticosteroids are not transported by P-gp to the same extent as systemic corticosteroids. However, they are able to induce P-gp production. Thus, inhaled corticosteroids may have greater interactions with other P-gp substrates, but P-gp itself is less likely to influence resistance to the drugs.

    Related items

    Showing items related by title, author, creator and subject.

    • Inhibition of P-glycoprotein - Mediated Efflux of Digoxinand Its Metabolites by Macrolide Antibiotics
      Hughes, Jeffery; Crowe, Andrew (2010)
      This study was conducted to determine the rate of P-glycoprotein (P-gp) mediated efflux of digoxin analogues and metabolites, and to assess the effects of macrolide antibiotics on this efflux. Bidirectional transport ...
    • The influence of passage number for Caco2 cell models when evaluating P-gp mediated drug transport
      Senarathna, Ganga; Crowe, Andrew (2015)
      Caco2 cells are a human adenocarcinoma cell line that forms tight junctions and are widely used to examine bidirectional drug transport as well as P-glycoprotein mediated efflux. Unfortunately Caco2 cell lines can be very ...
    • The current role for clinical and renal histological findings as predictor for outcome in Australian patients with lupus nephritis
      Nossent, J.; Raymond, W.; Kang, A.; Wong, D.; Ognjenovic, M.; Chakera, Aron (2018)
      © The Author(s) 2018. Objectives: To investigate the current demographic, clinical and histological characteristics of patients with lupus nephritis (LN) in Western Australia (WA) with regards to their predictive value ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.