Relationships between convulsive seizures and serum and brain concentrations of phenobarbital and zonisamide in mutant inbred strain EL mouse.

We evaluated the anticonvulsive effects of phenobarbital (PB) and zonisamide (ZNS) in the EL mouse, a strain that is highly susceptible to seizures. The concentration of each agent was analyzed in the serum and brain. PB suppressed the seizures dose-dependently, whereas even the higher dose of ZNS was ineffective in achieving a complete suppression. Serum and brain concentrations of these two drugs increased in proportion to the higher dose injected intraperitoneally. Brain concentration of PB was lower than the serum concentration, while the brain concentration of ZNS exceeded that in serum. Although serum concentration of ZNS was essential unchanged after the combined administration of PB and ZNS, the concentration of ZNS in brain tended to rise in proportion to the highly dose of PB. Combined administration was more effective than other treatment alone. Results indicated that brain concentration of ZNS especially after concomitant PB administration, were higher than that would be expected from the concentration of ZNS in serum.