Phenytoin metabolism in pregnancy

Approximately 45% of patients with epilepsy experience an increase in seizure frequency during pregnancy. Despite the availability of effective anticonvulsant medications, there has been no decrease in reported seizure frequency accompanying pregnancy in the past 35 years. The authors prospectively studied concentrations of phenytoin (DPH) and its metabolites in 5 patients throughout pregnancy and during the postpartum period. The concentrations of phenytoin, as well as both unconjugated and conjugated forms of its principal metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (4-OH-DPH), were measured in plasma and urine by a precise high-pressure liquid chromatography method. Four patients experienced a decrease in plasma DPH during gestation, 3 of whom developed seizures at a time of low plasma DPH concentration. Within the therapeutic range, small increments in dosage resulted in large increments in plasma DPH levels, and in the postpartum period high levels of DPH were encountered if the dosage was not reduced. As pregnancy progressed, there was a decrease in the percentage of the daily dosage of DPH excreted as 4-OH-DPH. Based on these observations, the authors conclude that 1) pregnancy is associated with altered DPH absorption or metabolism or both, and 2) periodic measurement of plasma DPH concentration is valuable when managing a pregnant epileptic patient.