Drug Transporters - Emerging Technologies
Posted on Fri, Dec 16, 2011 @ 10:59 AM
Drug Transporter Interactions
Review of In Vitro Approaches and Models
Drug transporters are increasingly being implicated as a source of drug–drug interactions (DDIs) and potential organ specific toxicity in humans and interactions with these membrane bound proteins are becoming increasingly important to assess during drug development as recent regulatory draft guidance reflects.
A review of current in vitro approaches to test for transporter-mediated interactions written by Guy Webber, Chief Scientist (In Vitro Sciences) at Quotient Bioresearch, has recently been published in Pharma Magazine, the Global magazine for the Pharmaceutical and Biopharmaceutical Industry. The review, entitled "Drug Transporters Emerging Technologies" discusses the advances in in vitro models for the assessment of drug transporter interactions and some of the major approaches being adopted.
Drug Transporters; Regulatory Landscape
For each transporter, it is recommended that in vitro testing is conducted to assess whether a new drug is either a substrate or an inhibitor of specified clinically relevant transporter proteins. The ITC (International Transporters Consortium) suggests decision trees for each of the recommended efflux and uptake transporters outlining how in vitro data should be viewed and the possible consequences for clinical assessment in vivo. Details of the transporters involved can be found in the full review.
In Vitro Models for Transporter Assessment
An accurate assessment of transporter interactions must take into account the cellular permeability of the test compound, as this will determine the appropriate in vitro model to use (generally, only sufficiently permeable molecules will be subject to efflux unless they undergo active uptake into the cell). Furthermore, compounds that undergo a degree of nonspecific binding may also be unsuitable for testing in cellular systems. A variety of models, therefore, have been developed and are currently used to test for interactions with drug transporters in vitro, which typically involve cellular and/or membrane‑based assays. The approaches outlined in the review focus on the major human efflux transporters, discussing methodology, and showing typical results obatined at Quotient.
It is becoming evident that assessment of transport related DDIs will become an increasingly important part of safety assessment during drug development and will form part of the clinical development strategy.
We look forward to the next meeting of the ITC (March 2012) and will post our interpretation of their recommendations.
Download the full review now
