Generalized seizure triggering threshold and serum phenobarbital levels during pregnancy in rats

In experiments using pregnant rats, the following results were noted: (a) Of the amygdaloid kindled rats, the generalized seizure triggering threshold of the pregnant group was significantly higher than that of the nonpregnant group. (b) Of the rats taking oral phenobarbital, 4 mg/kg once a day, there was no significant difference of serum levels between the pregnant group and the nonpregnant group. (c) Of the amygdaloid kindled rats taking oral phenobarbital, 4 mg/kg once a day, the generalized seizure triggering threshold of the pregnant group was significantly higher than that of the nonpregnant group. It may be suggested that, when the drug dose remains the same, the rise in threshold by gestational physiological changes antagonizes the fall in threshold by decreased serum levels of anticonvulsants because of increasing distribution volume due to increasing body weight during pregnancy.