Efflux Transporters and their Clinical Relevance

Title: Efflux Transporters and their Clinical Relevance

Volume: 5 Issue: 2

Author(s): V. Fischer, H. J. Einolf and D. Cohen

Affiliation:

Keywords: efflux transporters, p-glycoprotein, multi-drug resistance

Abstract: It is increasingly recognized that efflux transporters play an important role, not only in chemo protection e.g. multi-drug resistance, but also in the absorption, distribution, and elimination of drugs. The modulation of drug transporters through inhibition or induction can lead to significant drug-drug interactions by affecting intestinal absorption, renal secretion, and biliary excretion, thereby changing the systemic or target tissue exposure of the drug. Few clinically significant drug interactions that affect efficacy and safety are due to a single mechanism and there is considerable overlap of substrates, inhibitors, and inducers of efflux transporters and drug metabolizing enzymes, such as CYP3A. As well, genetic polymorphisms of efflux transporters have been correlated with human disease and variability of drug exposure. Accordingly, this review will discuss drug interactions and suitable probe substrates, as well as, the clinical relevance of the variability and modulation of efflux transporters and the exploitation of substrates as diagnostic tools. An update is given on inhibitors, which clinically reverse drug resistance and minimize the risk of metabolic interactions.

Cite this article as:

Fischer V., Einolf J. H. and Cohen D., Efflux Transporters and their Clinical Relevance, Mini-Reviews in Medicinal Chemistry 2005; 5 (2) . https://dx.doi.org/10.2174/1389557053402756