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Epilepsia. 2008 Jun;49(6):1075-80. Epub 2007 Dec 11.

Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy.

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1
Department of Medicine, Clinical Pharmacology Unit, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden. inger.ohman@ki.se

Abstract

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.

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