• blood–brain barrier;
  • efflux transport;
  • P-glycoprotein;
  • brain uptake;
  • microdialysis


Efflux transport at the blood–brain barrier (BBB) limits the brain tissue exposure to a variety of potential therapeutic agents, including compounds that are relatively lipophilic and would be predicted to permeate the endothelial lining of the brain microvasculature. Recent advances in molecular and cell biology have led to identification of several specific transport systems at the blood–brain interface. Refinement of classical pharmacokinetic experimentation has allowed assessment of the structural specificity of transporters, the impact of efflux transport on brain tissue exposure, and the potential for drug–drug interactions at the level of BBB efflux transport. The objective of this minireview is to summarize efflux transporter characteristics (location, specificity, and potential inhibition) for transport systems identified in the BBB. A variety of experimental approaches available to ascertain or predict the impact of efflux transport on net brain tissue uptake of substrates also are presented. The potential impact of efflux transport on the pharmacodynamics of agents acting in the central nervous system are illustrated. Finally, general issues regarding the role of identifying efflux transport as part of the drug development process are discussed. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1739–1753, 2003