IngentaConnect Plasma concentrations of lamotrigine and its 2-N-glucuronide meta...

Authors: Öhman, Inger¹; Beck, Olof¹; Vitols, Sigurd¹; Tomson, Torbjörn²

Source: Epilepsia, Volume 49, Number 6, June 2008 , pp. 1075-1080(6)

Abstract:

Summary

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.

Keywords: Epilepsy; Pregnancy; Lamotrigine; Pharmacokinetics; Glucuronidation

Document Type: Research article

DOI: 10.1111/j.1528-1167.2007.01471.x

Affiliations: 1: Department of Medicine, Solna, Clinical Pharmacology Unit 2: Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

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