Comparison of Ki and IC50 Values for Prototypical Inhibitors of ABC Transporters P-gp and BCRP
Ki values were determined for prototypical inhibitors of ABC transporters P-gp and BCRP with an experimental design incorporating multiple substrate and inhibitor concentrations in vesicles. The EMA’s Guideline on the Investigation of Drug Interactions (2012) recommends Ki values for evaluating transporter inhibition. The use of IC50 values is recommended only when Kideterminations are not possible. Although Ki values have been reported for inhibitors of various transporters, the methodology differs between labs and oftentimes relies on evaluation of a single probe substrate concentration combined with mathematical extrapolation.
These experiments were conducted to compare IC50 and Ki values determined in transporter-expressing membrane vesicles.