CNS Transporters and Drug Delivery in Epilepsy

Title:CNS Transporters and Drug Delivery in Epilepsy

Volume: 20 Issue: 10

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

Affiliation:

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

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.

Cite this article as:

Potschka Heidrun and Luna-Munguia Hiram, CNS Transporters and Drug Delivery in Epilepsy, Current Pharmaceutical Design 2014; 20 (10) . https://dx.doi.org/10.2174/13816128113199990461