Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period.
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.
Fotopoulou
Christina
C
Department of Obstetrics and Gynecology, Charité--University Hospital, Berlin, Germany. christina.fotopoulou@charite.de
Kretz
Rebekka
R
Bauer
Steffen
S
Schefold
J C
JC
Schmitz
Bettina
B
Dudenhausen
Joachim W
JW
Henrich
Wolfgang
W
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
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine