Unit

UNIT 7.13 Assessment of P-Glycoprotein Substrate and Inhibition Potential of Test Compounds in MDR1-Transfected MDCK Cells

  1. Kevin C. L. Lam,
  2. Ganesh Rajaraman

Published Online: 1 SEP 2012

DOI: 10.1002/0471141755.ph0713s58

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

C. L. Lam, K. and Rajaraman, G. 2012. Assessment of P-Glycoprotein Substrate and Inhibition Potential of Test Compounds in MDR1-Transfected MDCK Cells. Current Protocols in Pharmacology. 58:7.13:7.13.1–7.13.17.

Author Information

  1. NoAb BioDiscoveries, Mississauga, Ontario, Canada

Publication History

  1. Published Online: 1 SEP 2012

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.

Keywords:

  • cell permeability assay;
  • MDCK;
  • MDR1;
  • P-gp;
  • substrate;
  • inhibition;
  • bidirectional;
  • transport