Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

CNS Transporters and Drug Delivery in Epilepsy

Author(s): Heidrun Potschka and Hiram Luna-Munguia

Volume 20, Issue 10, 2014

Page: [1534 - 1542] Pages: 9

DOI: 10.2174/13816128113199990461

Price: $65

Abstract

Unfortunately, antiepileptic drug therapy fails to control seizure activity in a relevant percentage of epilepsy patients. Epidemiological data as well as findings in human epileptic tissue and in rodent models indicate that drug resistance is a multi-factorial phenomenon with various factors contributing to therapeutic failure. Enhanced efflux transport of antiepileptic drugs as a consequence of seizure-associated up-regulation of transporters such as P-glycoprotein constitutes one factor discussed in this context. Evidence exists that expression rates of P-glycoprotein correlate with drug response in rodent models and in patients. Moreover, add-on of a Pglycoprotein modulator proved to be efficacious in a rat model of drug-resistant epilepsy.

Further proof is obviously needed regarding the relative functional relevance of blood-brain barrier efflux for antiepileptic drug efficacy in epilepsy patients. Ongoing studies with positron emission tomography using transporter substrate radiotracers might provide further information. However, these studies also face major challenges considering the complexity of various factors affecting the kinetics of radiotracers in central nervous system pathologies.

Keywords: Seizure, blood-brain barrier, transporter, drug resistance, p-glycoprotein.


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy