Antiepileptic Drug Disposition in Pregnancy

  • MJ Eadie
  • FJE Vajda


The progressive physiological changes that occur in the female body during pregnancy, and their reversal in the weeks after the delivery of the foetus and placenta at the time of childbirth, have consequences for the body’s handling of drugs. The physiological changes have little effect on the absorption of the orally administered drugs, but the expanded extracellular fluid volume of pregnancy and the increasing bulk of the uterus and its contents have a diluting effect on circulating drug concentrations. Also, in later pregnancy, plasma protein concentrations decrease, resulting in a relative increase in plasma-unbound drug concentrations relative to total drug concentrations. Overall, the magnitude of these effects is small relative to the effects of pregnancy on drug elimination. Increased glomerular filtration during pregnancy increases the excretion of antiepileptic drugs that are cleared from the body predominantly as unchanged molecules, while the increasing circulating steroidal sex hormone concentrations of pregnancy induce formation of the liver enzymes that metabolise antiepileptic drugs that are cleared from the body by biotransformation. The overall result of these two processes is for circulating concentrations of antiepileptic drugs to fall relative to drug dose during pregnancy, potentially compromising the control of the seizure disorders for which the drugs have been prescribed.

After childbirth, antiepileptic drugs seem to enter maternal milk by a process of passive transfer along concentration gradients, with factors such as the fat and protein content of the milk affecting the drugs’ concentrations in that fluid. These concentrations are generally lower than those simultaneously present in maternal plasma.


Antiepileptic Drug Maternal Plasma Dose Ratio Maternal Body Plasma Water 
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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • MJ Eadie
    • 1
  • FJE Vajda
    • 2
  1. 1.Clinical Neurology and NeuropharmacologyUniversity of Queensland, and Honorary Consultant Neurologist, Royal Brisbane and Women’s HospitalBrisbaneAustralia
  2. 2.Department of Medicine and Neurology Director of the Australian Epilepsy and Pregnancy RegisterUniversity of Melbourne and Royal Melbourne HospitalMelbourneAustralia

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