Pharmacokinetic and pharmacodynamic markers and correlation studies for pharmacotherapy optimization of antiepileptic drugs

Project Details

Description

Pharmacoresistance remains a major problem in the treatment of the epilepsies today. In up to 30% of patients with epilepsy (especially temporal lobe epilepsy) the seizures persist despite the choice of an adequate antiepileptic drug (AED) and carefully monitored treatment1. A combination of pharmacodynamic (PD) and pharmacokinetic (PK) variations are considered to lay at the basis of refractory epilepsy. The "PD or target hypothesis" suggests that the pharmacological targets are rendered irresponsive or downregulated due to AED treatment and/or epileptogenic processes, leading to insufficient therapeutic effects. On the other hand, the "PK hypothesis" suggests that drug targets cannot be reached to a sufficient extent due to epilepsy-related suppressed AED distribution to the brain. A thorough characterisation of the PK and PD alterations is imperative to anticipate and adjust AED treatment strategies in order to suppress refractory seizures. Additionally, research towards antiepileptogenic and innovatie antiepileptic treatment approaches is necessary to reduce the percentage of refractory patients.

Aim:

1) Optimisation of antiepileptic pharmacotherapy via population PK/PD modelling.

2) Characterisation and modulation of blood-brain barrier (BBB) permeability during the acute, latent and recurrent stages of experimental post-status epilepticus (SE) chronic epilepsy.

3) Quantification and evaluation of post-SE variations in GABAA receptor subunit composition, neurodegenerative and -regenerative processes.

4) Evaluation of the therapeutic potential of the hippocampal monoaminergic system as an innovative target for the treatment of epilepsy.
AcronymFWOTM458
StatusFinished
Effective start/end date1/10/0530/09/14

Flemish discipline codes

  • Basic sciences

Keywords

  • pharmacology