Assessment of P‐Glycoprotein Substrate and Inhibition Potential of Test Compounds in MDR1‐Transfected MDCK Cells

Abstract P‐glycoprotein (P‐gp) is the most widely studied drug transporter due to its potential role in drug disposition and efficacy, and drug‐drug interactions (DDI). It is abundantly expressed in both the intestinal wall and blood‐brain barrier where it serves as a drug permeability barrier while simultaneously facilitating drug elimination in the liver and kidney. It is also abundantly expressed in tumors where it can facilitate the elimination of chemotherapeutics, a phenomenon known as multidrug resistance (MDR). Clinically relevant DDIs involving P‐gp are well documented; for example, the P‐gp substrate, digoxin, exhibits toxicity when co‐administered with a Pgp‐inhibitor. This makes it essential to screen new chemical entities early in development for their potential to be a substrate and/or inhibitor of P‐gp. Detailed in this unit is an in vitro protocol for assessing the P‐gp substrate and inhibition potential of test compounds using the MDCK MDR1 and MDCK WT cell lines. Curr. Protoc. Pharmacol . 58:7.13.1‐7.13.17. © 2012 by John Wiley & Sons, Inc.