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    Limited P-glycoprotein mediated efflux for anti-epileptic drugs.

    Access Status
    Fulltext not available
    Authors
    Crowe, Andrew
    Teoh, Y.
    Date
    2006
    Type
    Journal Article
    
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    Citation
    Crowe, Andrew and Teoh, Yee. 2006. Limited P-glycoprotein mediated efflux for anti-epileptic drugs.. Journal of Drug Targeting 14 (5): pp. 291-300.
    Source Title
    Journal of Drug Targeting
    DOI
    10.1080/10611860600720814
    ISSN
    1061-186X
    Faculty
    Faculty of Health Sciences
    School of Pharmacy
    URI
    http://hdl.handle.net/20.500.11937/8478
    Collection
    • Curtin Research Publications
    Abstract

    A variety of anti-epileptic drugs (AEDs) were tested for their ability to be transported by P-glycoprotein (P-gp) through Caco-2 monolayers using bi-directional (apical (Ap) to basolateral (Bas), and Bas to Ap) studies. Transport rates were equivalent in both directions for vigabatrin, gabapentin, phenobarbitone, lamotrigine and carbamazepine, being 0.7 × 10− 6, 0.1 × 10− 6, 34 × 10− 6, 36 × 10− 6 and 55 × 10− 6 cm/s, respectively. Phenytoin displayed a 20% increase in Ap to Bas transport, while topiramate and ethosuximide each had greater transport in the uptake direction, with both drugs showing no efflux. None of the transport rates for these drugs were affected by P-gp inhibitors. However, the efflux rate for acetazolamide was 3-fold higher than its uptake and this was significantly reduced by P-gp inhibitors. Thus, only one anti-epileptic, acetazolamide, was shown to be weak P-gp substrate, suggesting that P-gp efflux may not be a factor in relation to the development of resistance of epilepsy therapy.

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