Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy.
OBJECTIVE
To further characterize pregnancy-induced alterations in the pharmacokinetics of lamotrigine (LTG).


METHODS
Fifteen women treated with LTG were studied during 17 pregnancies. Complete trough blood samples from all trimesters and baseline > 1 month after delivery were available for 12 pregnancies (Group A), whereas, five contributed with samples only from the third trimester and baseline (Group B). High-performance liquid chromatography (HPLC) was used to determine LTG plasma concentrations, and liquid chromatography-mass spectrometry to assay the main metabolite 2-N-lamotrigine glucuronide (2-N-GLUC) in plasma.


RESULTS
In group A, the mean dose/plasma concentration ratio (D/C) of LTG at baseline after pregnancy was 66.5 +/- 17.9 (+/- SD) L/day and approximately 250% higher in late pregnancy. The mean lamotrigine-2-N-glucuronide/lamotrigine plasma concentration ratio (2-N-GLUC/LTG) was 0.349 +/- 0.141 (+/- SD) at baseline and 147% higher in late pregnancy. Taking group A and B together, the 2-N-GLUC/LTG ratio was 175% higher in the third trimester compared to baseline.


CONCLUSIONS
Our study confirms a significant decline in LTG plasma levels during pregnancy in women on monotherapy with LTG. An increased 2-N-GLUC/LTG ratio suggests that this decline may be related to an increased metabolism of LTG by glucuronidation.
Ohman
Inger
I
Department of Medicine, Clinical Pharmacology Unit, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden. inger.ohman@ki.se
Beck
Olof
O
Vitols
Sigurd
S
Tomson
Torbjörn
T
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D008658:Inactivation, Metabolic; D000077213:Lamotrigine; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000188:drug therapy; D011264:Pregnancy Trimesters; D012016:Reference Values; D014227:Triazines / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D014227:Triazines; C074259:lamotrigine 2-N-glucuronide; D000077213:Lamotrigine