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.