Pharmacokinetics of antiepileptic drugs during pregnancy.

During pregnancy, a number of physiologic changes occur that can affect the pharmacokinetics of antiepileptic drugs. Because of its nonlinear kinetics, phenytoin is most affected, with concentrations decreasing to half of prepregnancy values. Carbamazepine and valproate levels also decrease but to a lesser degree. Phenobarbital and primidone levels decrease as well. Some of the changes may be more apparent than real, however, because of changes in antiepileptic drug binding to plasma proteins. It is recommended that concentrations be measured frequently during pregnancy and dose adjustments made as needed. Unbound (free) levels should be measured when drugs known to alter binding are also being taken.