Abstracts

RATIONALE: We have recently demonstrated that levetiracetam (LEV; KEPPRA[reg]) markedly enhances the anticonvulsant properties of various antiepileptic drugs (AEDs) in audiogenic susceptible mice (Matagne et al., [italic]Epilepsia[/italic] 2001, 42(Suppl. 7):82). The current study investigated whether a supra-additive pharmacodynamic interaction also exists between LEV and several classical AEDs in amygdala-kindled rats, a preclinical model mimicking partial epilepsy in man.
METHODS: All experiments were conducted in fully amygdala-kindled male Sprague-Dawley rats (350 [ndash] 550 g; n=8). LEV and the classical AEDs were administered i.p. 60 and 30 min, respectively, before testing. Anticonvulsant effects were assessed by protective ED[sub]50[/sub] values against secondary generalized motor seizures (score 3, 4 or 5 on the Racine[scquote]s scale). Changes in the anticonvulsant potency ratio were expressed by the ratio between the ED[sub]50[/sub] value of the AED alone and the ED[sub]50[/sub] value obtained when combining different doses of a classical AED with one of two fixed doses of LEV (17 and 108 mg/kg).
RESULTS: Combining the lowest fixed dose of LEV (17 mg/kg) with valproate, clonazepam, phenobarbital and carbamazepine produced an increase in their anticonvulsant potency by a factor of 3, 4, 4 and 2, respectively. This increase was more important with the highest fixed dose of LEV (108 mg/kg) which produced factors of 9, 8, 4 and 2, respectively.
CONCLUSIONS: The present study confirms previous preclinical observations in audiogenic susceptible mice by showing that LEV markedly enhances the seizure suppression of various AEDs in amygdala-kindled rats. This supra-additive pharmacodynamic interaction suggests that the future medical management of partial epilepsy could benefit from combination therapy with LEV.
[Supported by: UCB S.A. Pharma Sector]; (Disclosure: Salary - UCB S.A.)