Dose-response population analysis of levetiracetam add-on treatment in refractory epileptic patients with partial onset seizures.
In this post hoc analysis, individual seizure counts from four double-blind trials of adjunctive treatment with levetiracetam were analyzed by non-linear mixed-effects modeling (NONMEM). First, a model was fitted to the individual count data assuming a Poisson distribution, in order to classify the patients as either improving or deteriorating from baseline. In the second stage, the dose-response relationship in improving patients was determined by fitting the data to an E(max) model including a placebo effect. The percentage of improvers was 59% on placebo and 73%, 74%, 77% and 73% on levetiracetam 1, 2, 3 and 4g/day, respectively. The ED(50) of 1408mg/day was close to the current WHO Defined Daily Dose of levetiracetam (1500mg). The maximum recommended dose of 3000mg/day was predicted to reduce seizures by >or=90% in 10% of improving patients. Age, gender, body weight, race, and number of concomitant antiepileptic drugs neither affected the percentage of responders nor the extent of change in seizure frequency from baseline.
Snoeck
Eric
E
Exprimo, Lummen, Belgium.
Stockis
Armel
A
D000927:Anticonvulsants / Q000008:administration & dosage*; D017326:Clinical Trials, Phase III as Topic; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D017711:Nonlinear Dynamics; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012640:Seizures / Q000188:drug therapy*
D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam