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

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.

Keywords::

• uptake
• efflux
• biological availability
• genes
• MDR
• P-glycoprotein
• multidrug resistance–associated protein 2
• null mice
• humanized mice

Acknowledgement

Preparation of this review was supported by ITI Sciences, Dundee, United Kingdom as part of its Transgenetic Screening and Safety (TSM) programme.

Declaration of interest: The authors report no financial conflicts of interest. The authors alone are responsible for the content and writing of this paper.