Evidences for pharmacokinetic interaction of riluzole and topiramate with pilocarpine in pilocarpine-induced seizures in rats

Riluzole (4 mg/kg) lowered plasma and brain concentration of pilocarpine administered at a dose of 400 mg/kg from 168.0 ± 8.6 to 75.3 ± 19.9 μg/ml and from 193.7 ± 6.6 to 97.0 ± 26.1 μg/g, respectively.Topiramate (200 mg/kg) increased plasma and brain concentration of pilocarpine administered at a dose of 300 mg/kg from 78.1 ± 2.9 to 106.0 ± 6.8 μg/ml and from 138.4 ± 5.0 to 155.2 ± 5.1 μg/g, respectively. It seems that both anticonvulsant effect exerted by riluzole and proconvulsant effect exerted by topiramate in pilocarpine model of seizures are due to a pharmacokinetic interaction. Therefore, we postulate that the concentration of pilocarpine should be measured routinely whenever the anticonvulsant effect of drugs is determined in the pilocarpine model of seizures.