AAPS Transporter 2013 - Inhibitors of Uptake Transporters

AAPS Transporter 2013 - Inhibitors of Uptake Transporters

Published:  05 March 2013

Comparison of Ki and IC50 Values for Prototypical Inhibitors of Uptake Transporters

Ki values were determined for prototypical inhibitors of uptake transporters with an experimental design incorporating multiple substrate and inhibitor concentrations. The EMEA’s Guideline on the Investigation of Drug Interactions (2012) recommends that Ki values be calculated for the inhibition of a transporter by investigational drugs and IC50 values used only when a Ki value is not possible. Although Ki values have been reported for inhibitors of various uptake transporters, the methodology differs between labs and oftentimes relies on evaluation of a single concentration of the probe substrate combined with a mathematical extrapolation of the Ki value. The present study was designed to compare IC50 values to Ki values experimentally determined with four concentrations of both probe substrate and inhibitor.