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 pregn ancies (cases) of 70 patients with epilepsy. Seventy-seven cases were treated with monotherapy, which in 70 cases consisted of carbamazepine (CBZ) or phenytoin (PI-IT). Dosage was kept constant unless poor seiz ure control prompted an increase. Plasma concentrations were determine d 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 pregna ncy 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. T otal CBZ concentration was slightly lower during the third trimester a s compared with baseline, whereas free concentration was unchanged. In contrast, PHT levels decreased steadily as pregnancy progressed. Tota l plasma concentration was 39% of baseline during the third trimester, whereas free PHT concentration decreased far less, being 82% of basel ine level during the third trimester. No clear-cut relation could be d emonstrated between seizure control and plasma concentrations, which m ay be explained by the limited changes in free AED concentrations and the small number of cases with an increased seizure frequency. Our res ults indicate that total plasma concentrations may be misleading and t hat monitoring of free concentrations, in particular of PHT concentrat ions, may be advantageous during pregnancy.