Pharmacokinetics of antiepileptic drugs in pregnancy

Abstract

A substantial proportion of women with epilepsy experience seizure deterioration during pregnancy. This is most likely explained by a drop in plasma levels of antiepileptic drugs (AEDs) as a consequence of altered drug pharmacokinetics. It has been known for many years that gestation induces the elimination of standard AEDs (phenytoin, barbiturates, carbamazepine and valproate). In general, newer AEDs have more simple pharmacokinetic properties and it should, therefore, be expected that the pharmacokinetics of these drugs are influenced in a simpler manner by physiological changes, such as pregnancy. However, within the last few years it has been established that the elimination of several newer AEDs is significantly accelerated during pregnancy. This is particularly the case for glucuronidated AEDs (i.e., lamotrigine) and the pharmacological active metabolite of oxcarbazepine (metabolite 10-hydroxycarbazepine). Recent observations show it is probable that the elimination of levetiracetam is also increased during pregnancy. Pharmacokinetic alterations during pregnancy show wide interindividual variability and the effects on the plasma levels are mostly unpredictable. Regular routine drug monitoring during pregnancy is therefore recommended. The future perspective involves the development of pharmacogenetic charting, which may assist in providing an individualized treatment strategy and refine preconceptional therapeutic planning to ensure the best possible health for the mother and developing child.