The anticonvulsant properties of phenytoin (DPH) in combination with phenobarbital (PB) were studied using maximal electroshock seizures in rats. ED50 values for each drug were determined and combinations formulated according to the method of Weaver. Brain concentrations of DPH and PB, measured by GLC in 93 rats, were significantly higher in protected animals (p < 0.01). In combination, each drug was present in a lower concentration (p < 0.01) but the sum of the two was the same as in single drug treatment. These two drugs are thus equipotent and additive in combination. Apparent potentiation in the rat was due to decreased elimination of DPH in the presence of PB. Theoretical drug concentrations in human cerebral cortex were computed from the steady state plasma levels of 187 carefully monitored seizure patients.
|Published - Jan 1 1975