Drug efflux pumps: challenges and opportunities. 14-18 November 1999, New Orleans, LA, USA.

A symposium entitled 'Drug efflux pumps: challenges and opportunities' addressed the detection and functional characterization of drug efflux pumps, their influence on the cytochrome P450 (CYP450) system and their role in blood-brain barrier (BBB) permeability. Drug efflux pumps utilize ATP as the energy source in exporting solutes, and belong to the family of ATP-binding cassette transporters (ABC transporters). P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) are members of this family of transporters. These transporters are overexpressed in cancer cells leading to decreased drug accumulation and hence drug resistance. Another causative factor for drug resistance is increased elimination mechanisms, metabolism by CYP450 enzymes being the most important. The multidrug resistance gene (mdr) is a key determinant in the expression of CYP3A enzymes, the most predominant subclass of CYP450. New techniques are being developed to identify and characterize drug efflux pumps, the latest being gamma-scintigraphy and hypertonic saline (HTS). Efflux pumps play a major role in restricting the drug transport across the BBB. Currently, structural domains that are responsible for the functional activity of the efflux proteins are being investigated to design better inhibitors for drug efflux pumps.