title: Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Charité--University Hospital, Berlin, Germany. christina.fotopoulou@charite.de
authors.forename: Christina
authors.initials: C
authors.lastname: Fotopoulou
authors.forename: Rebekka
authors.initials: R
authors.lastname: Kretz
authors.forename: Steffen
authors.initials: S
authors.lastname: Bauer
authors.forename: J C
authors.initials: JC
authors.lastname: Schefold
authors.forename: Bettina
authors.initials: B
authors.lastname: Schmitz
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Dudenhausen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Henrich
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D007231:Infant, Newborn / Q000097:blood* / Q000378:metabolism; D007774:Lactation / Q000187:drug effects; D000077213:Lamotrigine; D008895:Milk, Human / Q000737:chemistry; D049590:Postpartum Period / Q000097:blood; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011446:Prospective Studies; D013997:Time Factors; D014227:Triazines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine