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One pregnancy out of 200 occurs in a woman taking antiepileptic drugs (AEDs), which means that epilepsy is the most common neurological disorder that requires continuous medical treatment during pregnancy. Although 90-95% of women with epilepsy experience an uneventful pregnancy with the delivery of a normal child, the complication rate is two- to threefold compared with the general population.
The traditional dilemma of the prescribing physician is to balance the risk of the teratogenic potential of the AEDs against the risk of seizure deterioration. Teratogenicity is related to the type of AED, high doses of the drugs and to polytherapy, whereas seizure deterioration is related to a drop in plasma concentration of the drug. It has been established that 15-37% of women with epilepsy experience seizure deterioration during pregnancy [1-3]. Uncontrolled seizures may be hazardous for the mother and fetus, and even a single seizure recurrence in a seizure-free woman may have detrimental psycho-social consequences.
Ideally, the treatment should be individualized for each patient to ensure that the treatment is optimally adjusted before conception. Knowledge and understanding of the pharmacokinetic variability of the specific AED during pregnancy is essential to determine the best practical treatment strategy and ensure optimal seizure control without dose-related adverse or toxic effects.
Pregnancy-induced pharmacokinetic factors
As the pregnancy advances, complex physiological changes influence the pharmacokinetic processes of drug absorption, distribution, metabolism and elimination.
Absorption
AEDs are generally administrated orally and are absorbed in the gastrointestinal canal. Pregnancy induces alterations in gastric and intestinal emptying time, and there is a significant reduction in gastric acid secretion, which leads to an increase in gastric pH. Theoretically, this may influence the bioavailability of AEDs, although this has not been shown in clinical studies.
Distribution
Total body water is increased by approximately 7-8 l, leading to plasma volume expansion of up to 50%, which potentially reduces the plasma concentration of AEDs.
Metabolism & elimination
The most important pregnancy-related pharmacokinetic alterations are decreased binding capacity to plasma proteins and enhanced drug elimination. Most AEDs are acidic or neutral and are bound to plasma proteins. The pregnancy-induced increased secretion of estrogen and progesterone stimulates hepatic microsomal enzyme activity and results in a higher rate of metabolism of certain drugs, such as phenytoin and barbiturates. Although...