Back to Journals » Drug Design, Development and Therapy » Volume 7

P-glycoprotein alters blood–brain barrier penetration of antiepileptic drugs in rats with medically intractable epilepsy

Authors Ma A, Wang C, Chen Y, Yuan W, Hu Z

Received 6 August 2013

Accepted for publication 20 September 2013

Published 3 December 2013 Volume 2013:7 Pages 1447—1454


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Aimei Ma,1,* Cuicui Wang,2,3,* Yinghui Chen,2,3 Weien Yuan4

1Department of Neurology, The People's Hospital of Shanxi Province, Taiyuan, 2Department of Neurology, Jinshan Hospital, Fudan University, 3Department of Neurology, Shanghai Medical College, Shanghai, 4School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China

*These authors contributed equally to this work

Abstract: P-glycoprotein is one of the earliest known multidrug transporters and plays an important role in resistance to chemotherapeutic drugs. In this study, we detected levels of P-glycoprotein and its mRNA expression in a rat brain model of medically intractable epilepsy established by amygdala kindling and drug selection. We investigated whether inhibition of P-glycoprotein affects the concentration of antiepileptic drugs in cortical extracellular fluid. We found that levels of P-glycoprotein and its mRNA expression were upregulated in epileptic cerebral tissue compared with cerebral tissue from normal rats. The concentrations of two antiepileptic drugs, carbamazepine and phenytoin, were very low in the cortical extracellular fluid of rats with medically intractable epilepsy, and were restored after blockade of P-glycoprotein by verapamil. These results show that increased P-glycoprotein levels alter the ability of carbamazepine and phenytoin to penetrate the blood–brain barrier and reduce the concentrations of these agents in extracellular cortical fluid. High P-glycoprotein levels may be involved in resistance to antiepileptic drugs in medically intractable epilepsy.

Keywords: P-glycoprotein, medically intractable epilepsy, antiepileptic drugs, amygdala kindling, verapamil

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]