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