Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy
Article first published online: 11 DEC 2007
© 2008 International League Against Epilepsy
Volume 49, Issue 6, pages 1075–1080, June 2008
How to Cite
Öhman, I., Beck, O., Vitols, S. and Tomson, T. (2008), Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy. Epilepsia, 49: 1075–1080. doi: 10.1111/j.1528-1167.2007.01471.x
- Issue published online: 11 DEC 2007
- Article first published online: 11 DEC 2007
- Accepted February 11, 2007; Online Early publication December 12, 2007.
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.
Conclusion: 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.