Effects of pregnancy on antiepileptic drug utilization

Pregnancy is associated with characteristic changes in the disposition of antiepileptic drugs; recent findings on this aspect of drug utilization are presented. In one study involving 48 pregnancies, the mean level-dose ratio of phenytoin decreased by 34%. In another study of 111 patients, phenytoin clearance increased gradually over the first 32 weeks of pregnancy and reached twice the preconception value. In two studies with phenobarbital, levels tended to decrease, although this effect was less pronounced than for phenytoin. Similarly for primidone, pregnancy had little effect on steady-state levels; however, levels of phenobarbital formed from primidone exhibited large decreases during pregnancy followed by increases after delivery. This effect was quite consistent. Carbamazepine clearance tended to increase to a relatively small extent. Limited data indicate that valproate levels decrease by 30 to 40% during pregnancy. The mechanisms responsible for these effects have not been elucidated and possibly include decreased bioavailability or compliance, increased metabolic clearance, or decreased plasma protein binding. Since the patient at risk of an increase in seizure frequency cannot be identified prior to conception, therapeutic monitoring is imperative during and after pregnancy.