Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior

Lesley A. Stanley, Brian C. Horsburgh, Jillian Ross, Nico Scheer, C. Roland Wolf

    Research output: Contribution to journalReview article

    24 Citations (Scopus)

    Abstract

    In this paper, we evaluate methodologies and null mouse models used to study drug transporter function in vitro and in vivo. P-glycoprotein and MRP null mice have been used to examine many aspects of xenobiotic distribution and bioavailability. Their advantage over conventional models is that they allow the exclusion of transporters from a particular process; however, they cannot be used to study the activity of the transporter that has been deleted. Use of humanized mice permits a logical progression from phenomena in wild-type mice via the effects of removing the mouse transporter to the consequences of replacing it with its human counterpart.

    Original languageEnglish
    Pages (from-to)27-65
    Number of pages39
    JournalDrug Metabolism Reviews
    Volume41
    Issue number1
    DOIs
    Publication statusPublished - Feb 2009

    Keywords

    • uptake
    • efflux
    • biological availability
    • genes, MDR
    • P-glycoprotein
    • multidrug resistance-associated protein 2
    • null mice
    • humanized mice
    • BLOOD-BRAIN-BARRIER
    • MDR1A P-GLYCOPROTEIN
    • MULTIDRUG-RESISTANCE PROTEIN
    • CENTRAL-NERVOUS-SYSTEM
    • ARTIFICIAL MEMBRANE-PERMEABILITY
    • DOUBLE KNOCKOUT MICE
    • ABSORPTION IN-VITRO
    • WILD-TYPE MICE
    • ORAL BIOAVAILABILITY
    • EFFLUX TRANSPORTERS

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