RT Journal Article
SR Electronic
T1 Perspective on the application of microphysiological systems to drug transporter studies
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP dmd.118.082750
DO 10.1124/dmd.118.082750
A1 Pedro Caetano-Pinto
A1 Simone H Stahl
YR 2018
UL http://dmd.aspetjournals.org/content/early/2018/08/22/dmd.118.082750.abstract
AB Transmembrane flux of a drug within a tissue or organ frequently involves a complex system of transporters from multiple families that have redundant and overlapping specificities. Current in vitro systems poorly represent physiology, with reduced expression and activity of drug transporter proteins, therefore, novel models that recapitulate the complexity and interplay among various transporters are needed. The development of microphysiological systems that bring simulated physiological conditions to in vitro cell culture models have enormous potential to better reproduce the morphology and transport activity across several organ models especially in tissues like the liver, kidney, intestine or the blood-brain-barrier where drug transporters play a key role. The prospect of improving the in vitro function of organ models highly prolific in drug transporters holds the promise of implementing novel tools to study these mechanisms with far more representative biology than before. In this short review we exemplify recent developments in the characterization of perfused microphysiological systems involving the activity of drug transporters. Further, we analyse the challenges and opportunities for the implementation of such systems in the study of transporter-mediated drug disposition and the generation of clinically relevant physiology based in silico models incorporating relevant drug transport activity.