Epilepsy and pregnancy: a prospective study of seizure control in relation to free and total plasma concentrations of carbamazepine and phenytoin.

Seizure control and plasma concentrations of antiepileptic drugs (AEDs) were determined in a prospective, population-based study of 93 pregnancies (cases) of 70 patients with epilepsy. Seventy-seven cases were treated with monotherapy, which in 70 cases consisted of carbamazepine (CBZ) or phenytoin (PHT). Dosage was kept constant unless poor seizure control prompted an increase. Plasma concentrations were determined at monthly intervals throughout pregnancy and compared with baseline levels obtained at least 10 weeks postpartum. Both free and total CBZ and PHT concentrations were analyzed. Seizure frequency during pregnancy for the group as a whole was not different as compared with the 9 pregestational months and was unaltered or improved in 85% of cases. Total CBZ concentration was slightly lower during the third trimester as compared with baseline, whereas free concentration was unchanged. In contrast, PHT levels decreased steadily as pregnancy progressed. Total plasma concentration was 39% of baseline during the third trimester, whereas free PHT concentration decreased far less, being 82% of baseline level during the third trimester. No clear-cut relation could be demonstrated between seizure control and plasma concentrations, which may be explained by the limited changes in free AED concentrations and the small number of cases with an increased seizure frequency. Our results indicate that total plasma concentrations may be misleading and that monitoring of free concentrations, in particular of PHT concentrations, may be advantageous during pregnancy.