Effects of pregnancy on seizure threshold and the disposition and efficacy of antiepileptic drugs in the mouse.

The effects of pregnancy on seizure excitability as well as antiepileptic drug disposition and efficacy were studied in the mouse during late gestation. Phenytoin and carbamazepine concentrations in brain were increased in pregnant animals, which was related to increased free concentrations in plasma. Little changes were observed for valproic acid and phenobarbital. The seizure threshold in untreated pregnant mice was significantly higher than in the nonpregnant group. The efficacy of carbamazepine and valproic acid in the pregnant animals was increased as compared to the control group; little changes were observed for phenobarbital and phenytoin. Our study indicates that - in contrast to the general clinical opinion - pregnancy has little influence or even a slight beneficial effect on the seizure propensity as well as the efficacy of antiepileptic drugs.