P-glycoprotein-mediated efflux transport of anticancer drugs at the blood-brain barrier

Ther Drug Monit. 1998 Oct;20(5):588-90. doi: 10.1097/00007691-199810000-00024.


Several lipophilic, cytotoxic drugs, or both, (including anticancer drugs [Vinca alkaloids, doxorubicin, cyclosporin A, and digoxin]) have proven to be actively effluxed by P-glycoprotein (P-gp) expressed at the luminal membrane of the brain capillary endothelial cells, resulting in the very low apparent blood-brain barrier (BBB) permeation of these P-gp substrates from the blood circulating to the brain. In rats inoculated with 9L-glioma cells into the brain, the endothelial cells of tumor-associated vessels allowed easy penetration of anticancer drugs (ranimustine and doxorubicin) in tumor regions, although the normal BBB function still operated at the normal brain region to provide a barrier to the accumulation of P-gp substrates. A detailed knowledge of the BBB function would be very helpful in developing improved delivery systems of anticancer drugs to brain tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacokinetics*
  • Biological Transport, Active
  • Blood-Brain Barrier*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Cell Membrane Permeability
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Humans


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents