gms | German Medical Science

In 20% of patients, the treatment of epilepsies is commonly known to be unsatisfactory. This may be due not only to a lack of efficiency of the antiepileptic drugs (AED) but also to pharmaokinetic problems. The aim of the present investigation was to analyze the spatial distribution of AED in the extracellular space of the temporal cerebral cortex at different sites. By using intraoperative microdialysis (IOMD) extracellular fluid was obtained from patients during resection of epileptic foci.

The concentrations of carbamazepine (n=9 pat.), 10-hydroxy-carbazepine (the main metabolite of oxcarbazepine) (n=6 pat.), lamotrigine (n=6), levetiracetam (n=3 pat.), topiramate or phenytoin (both as multiple drugs treatment) were determined in-vivo using one to four catheters (n=57 catheters) during IOMD. From 2000-2004, altogether 24 pharmacoresistant epileptic patients (14f, 10m) ranging in age from 15 to 54 years were studied. In a first series, IOMD samples 40 minutes after the beginning of the microdialysis (flow rate of perfusion fluid: 1μl/min) and in a second series continuous measurements 25, 30, 35 and 40 minutes from the beginning of microdialysis were evaluated (flow rate: 2μl/min).

CBZ and 10-OH-CZ were compared because indication and effect were similar. From a statisitical viewpont, the two substance groups together (n=15) comprise 63% of the patients. Compared to the correlation between serum_f and concentrations in total brain tissue, the correlation between serum_f and individual ECS concentrations was obviously lower for CBZ (r=0.41), 10-OH-CZ (r=0.42). This is also true when the mean ECS concentration was taken for each patient instead of single values:for CBZ (r=0.64), 10-OH-CZ (r=0.62).

The data demonstrate that concentrations of antiepileptic drugs(AED) vary considerably at different sites in the ECS of cortical regions. This could be an explanation for therapy resistance at least in some of the patients suffering from epilepsy.