P-glycoprotein-mediated efflux transport of anticancer drugs at the blood-brain barrier.
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.
Department of Pharmacobio-Dynamics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
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Tsuji
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents