Abstracts

To evaluate the time to onset of levetiracetam[apos]s (LEV. Keppra[reg]) clinical effects and correlate this with LEV daily serum concentrations, using therapeutic intensive seizure analysis (TISA), in pharmacoresistant focal epilepsies with LEV used as add-on therapy. Adult patients (age [gt]16 yrs) with pharmacoresistant focal epilepsy entering presurgical evaluation at the Epilepsy Center, Erlangen were enrolled. Eligible patients taking no more than 1 AED, with [ge]2 seizures during a 48-hour baseline phase, were randomised to 7-days treatment with either LEV or placebo. LEV was initiated as add-on therapy at 1000 mg on Day 1, titrating to 2000 mg from Day 2; serum concentrations were monitored daily 1 hour after dosing. Continuous 24 hour video-EEG recording was used to monitor seizure number (N/24h) and duration (D/24h) per 24 hours. 23 patients completed the study (LEV, n=11; placebo, n=12). 7 patients taking LEV and 2 taking placebo achieved seizure freedom during the treatment phase. Intergroup comparison of the N/24h and D/24h reductions from baseline to treatment phases favoured LEV (p[lt]0.05). LEV significantly inhibited D/24h from Day 2 (p=0.013) with a more marked effect from Day 3 (p=0.009). There was a linear relationship between daily LEV dose and serum concentration; steady state concentration being reached 72 hours after drug initiation. The present study quantified the antiepileptic effect of LEV in focal epilepsies relative to its serum concentration. For the first time, direct measurement has proven the onset of action of LEV to be 2 days after drug initiation. (Supported by UCB Pharma, Germany.)