The Therapeutic Drug Monitoring Unit was successfully relocated to the Chalfont Centre for Epilepsy in June 2007.

Antiepileptic drug polytherapy is the treatment regimen for many patients. However, the rational for choosing a particular combination is empirical. We continue our work to identify rational antiepileptic drug combinations that may prove particularly efficacious.

Pharmacodynamic and pharmacokinetic characterisation of conventional and newly licensed antiepileptic drug combinations

N Ratnaraj, P Patsalos
Collaborator: S Czuczwar (Medical University of Lublin, Poland)

We continue our work in this area and have began new studies to investigate the pharmacodynamic, pharmacokinetic and adverse effect profiles of antiepileptic drug (AED) combination whose mechanism of action relates specifically to GABA. These include vigabatrin, gabapentin and tiagabine. Seizures are recorded by use of the mouse maximal electroshock (MES) and pentylenetetrazole (PTZ) seizure models. Drug related adverse effects are determined by use of the chimney test (a measure of motor impairment) and the step-through passive avoidance task (a measure of learning and retrieval) and these data are being analysed by use of isobolography.

Population pharmacokinetics of levetiracetam

S Ghattaura, N Ratnaraj, M Walker, L Sander, P Patsalos. Collaborator: A Thomson (University of Glasgow )

Population pharmacokinetic data are an invaluable resource as they provide information which can enhance the therapeutic use of a drug. We are investigating levetiracetam, a new generation antiepileptic drug.

Our database is now closed and we have collected several thousands of data which are being analysed using a population pharmacokinetic analysis model and covariant analysis. The pharmacokinetics of levetiracetam and other new antiepileptic drugs are being investigated in terms of drug absorption, distribution, metabolism and excretion and inter-relationships between dose/blood levels and efficacy and dose/blood levels and adverse effects. We are seeking to identify which clinical factors are most important for levetiracetam use in patients with epilepsy, and thus determine optimal treatment strategies.

New anti-epileptic drugs

JW Sander, MJ Koepp , A Yuen, P Patsalos

We continue to attempt to improve antiepileptic drug treatment.
We are currently assessing the long-term retention, a composite measure of safety and efficacy, of the recently launched antiepileptic drugs, pregabalin and zonisamide. This assessment is important in order to find the correct place of these drugs in the antiepileptic armamentarium. We are also continuing to assess the potential antiepileptic efficacy of the free-fatty acid Omega-3. We are actively involved in the development of alternatives to the use of rectal diazepam as a rescue treatment for serial seizures and status epilepticus.

S Shorvon, S Smith, JW Sander

We are exploring the potential of intranasal clonazepam in the treatment of acute seizures in a multicentre project.

Assessment of general health status in Chalfont residents using biomarkers

A Yuen, G Bell, M Koepp, P Patsalos, JW Sander

Current data suggest that reducing the markers of free radical damage or increasing antioxidant capacity might be expected to reduce seizures.

Physical and biochemical health measures were collected from approximately half of all Chalfont residents in 2006 and 2007. A comparison of the health measures in 2006 with the UK general population showed that the Chalfont residents had increased weight, BMI, waist, waist-hip ratio, CRP (C-reactive protein, values in the normal range are markers for CVD and all cause mortality); but surprisingly a lower BP and HbA1c (a measure of long term blood glucose levels and a potent predictor of all cause mortality). These results are being written up for publication.

Erythrocyte and plasma fatty acid profiles in patients with epilepsy

A Yuen, JW Sander, D Flugel, P Patsalos, G Bell, M Koepp

The red blood cell and plasma fatty acid profiles from the residents in Chalfont who took part in the double blind omega-3 supplementation study were further analysed and the results were written up for publication. The results suggest that CBZ appears to lower Omega-3 Index (a risk factor for CHD mortality) whilst oxcarbazepine appears to be associated with a higher Omega-3 Index.

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