Journal
DRUG METABOLISM REVIEWS
Volume 41, Issue 1, Pages 27-65Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/03602530802605040
Keywords
uptake; efflux; biological availability; genes, MDR; P-glycoprotein; multidrug resistance-associated protein 2; null mice; humanized mice
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Funding
- Cancer Research UK [10822] Funding Source: Medline
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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.
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