alexa Drug efflux transporters in the CNS.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Sun H, Dai H, Shaik N, Elmquist WF

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Abstract The central nervous system (CNS) contains important cellular barriers that maintain homeostasis by protecting the brain from circulating toxins and through the elimination of toxic metabolites generated in the brain. The barriers that limit the concentration of toxins and xenobiotics in the interstitial fluids of the CNS are the capillary endothelial cells of the blood-brain barrier (BBB) and the epithelial cells of the blood-cerebrospinal fluid barrier (BCSFB). Both of these barriers have cellular tight junctions and express transport systems which serve to actively transport nutrients into the brain, and actively efflux toxic metabolites and xenobiotics out of the brain. This review will focus on the expression and function of selected drug efflux transporters in these two barriers, specifically the multidrug resistance transporter, p-glycoprotein, and various organic anion transporters, such as multidrug resistance-associated proteins, organic anion transporter polypeptides, and organic anion transporters. These transport systems are increasingly recognized as important determinants of drug distribution to, and elimination from, different compartments of the CNS. Consequences of drug efflux transporters in barriers of the CNS include limiting the distribution of substrates that are beneficial to treat CNS diseases, and increasing the possibility of drug-drug interactions that may lead to untoward toxicities. Therefore, the study of these transporters is important in examining the various determinants of drug delivery to the CNS.
This article was published in Adv Drug Deliv Rev and referenced in Journal of Bioequivalence & Bioavailability

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