Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period

Epilepsy Res. 2009 Jul;85(1):60-4. doi: 10.1016/j.eplepsyres.2009.02.011. Epub 2009 Mar 9.

Abstract

Purpose: To prospectively analyse the pharmacokinetics of lamotrigine (LTG) during pregnancy and lactation in a consecutive series of epileptic pregnant women.

Methods: Nine women on LTG-monotherapy were studied during pregnancy, delivery and lactation, until a mean of 3 weeks postpartum. Maternal blood samples were available from all trimesters as well as umbilical cord blood samples of the newborn 24 and/or 48 h postpartum. In 4 cases we additionally determined the LTG-concentration in breast milk.

Results: The median LTG-clearance was elevated by 197% during the first trimester, 236% and 248% during the second and third trimester respectively. A maximum of 264% was reached at delivery. An average LTG-dose increase by 250% had to be undertaken in order to obtain therapeutic serum levels. In puerperium LTG-clearance decreased again to reach the initial concentrations approximately at the third week postpartum. The median LTG-concentration ratio of the umbilical cord blood to maternal serum was 1.01 (range: 0.56-1.42), while the median LTG-concentration ratio of breast milk to maternal serum was 0.59 (range: 0.35-0.86).

Discussion: Our study confirms the therapeutic relevant changes of LTG-clearance during pregnancy and lactation in women on LTG-monotherapy. Since LTG crosses the placenta, a close monitoring of both mother and newborn is indispensable.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Dose-Response Relationship, Drug
  • Epilepsy / drug therapy*
  • Female
  • Fetal Blood / chemistry
  • Humans
  • Infant, Newborn / blood*
  • Infant, Newborn / metabolism
  • Lactation / drug effects
  • Lamotrigine
  • Milk, Human / chemistry
  • Postpartum Period / blood
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Prospective Studies
  • Time Factors
  • Triazines / pharmacokinetics
  • Triazines / pharmacology
  • Triazines / therapeutic use*
  • Young Adult

Substances

  • Anticonvulsants
  • Triazines
  • Lamotrigine