Effects of pregnancy and contraception on lamotrigine disposition: new insights through analysis of lamotrigine metabolites

Seizure : the Journal of the British Epilepsy Association
I OhmanTorbjörn Tomson

Abstract

To investigate possible underlying mechanisms for alterations in lamotrigine (LTG) kinetics by gestation and use of contraceptives. Plasma concentrations of LTG and its main metabolite lamotrigine-2-N-glucuronide (2-N-GLUC) were measured in 31 women on LTG taking combined oral contraceptives (COC), in 12 with contraceptive intrauterine devices containing levonorgestrel (CIUD), and in 20 on LTG without hormonal contraception (controls). We also measured the levels of LTG and 2-N-GLUC in plasma and urine in eight women during pregnancy, and up to three months postpartum. LTG levels in plasma were measured by high-performance liquid chromatography method (HPLC) and N-2-GLUC in urine and plasma and LTG in urine by liquid chromatography-mass spectrometry (LC/MS). There were no significant differences in LTG dose/concentration (D/C), or N-2-GLUC/LTG ratios between women with CIUD and controls. In contrast, compared to controls, the LTG D/C ratio was 56% higher in women taking COC (mean+/-SD, 83+/-47 versus 53.0+/-24.2; p<0.01) and N-2-GLUC/LTG ratio 82% higher in women taking COC (mean 0.477+/-0.212 SD versus 0.262+/-0.127; p<0.0003. The 2-GLUC/LTG ratios were 154% higher in plasma and 122% higher in urine in late pregnancy compared ...Continue Reading

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Citations

May 24, 2014·Neurobiology of Disease·Emilio PeruccaTorbjörn Tomson
Oct 5, 2014·Seminars in Perinatology·Yang ZhaoRaman Venkataramanan
Jan 19, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nina Isoherranen, Kenneth E Thummel
Jun 18, 2009·Current Opinion in Neurology·Anne Sabers, Torbjörn Tomson
Nov 9, 2011·Advanced Drug Delivery Reviews·Cecilie Johannessen LandmarkTorbjörn Tomson
Mar 26, 2011·Epilepsy Research·Cecilie Johannessen LandmarkSvein I Johannessen
May 24, 2011·Epilepsy Research·Medine Idrizoglu GulcebiFiliz Yılmaz Onat
Dec 8, 2010·Contraception·Mary E GaffieldC Rhoda Lee
Aug 17, 2010·Epilepsy & Behavior : E&B·Torbjörn TomsonInger Ohman
Mar 31, 2009·Epilepsy & Behavior : E&B·Anne Sabers
Jun 6, 2009·Epilepsia·Anne Sabers, Vaiva Petrenaite
May 13, 2009·BJOG : an International Journal of Obstetrics and Gynaecology·S P WalkerS F Berkovic
Nov 10, 2011·Pharmacoepidemiology and Drug Safety·Cecilie Johannessen Landmark, Svein I Johannessen
Jun 3, 2014·Annals of Clinical and Translational Neurology·Akshanth R PolepallyAngela K Birnbaum
Jun 9, 2014·Seizure : the Journal of the British Epilepsy Association·Arne Reimers
Sep 3, 2013·Epilepsy & Behavior : E&B·Ilse WegnerDick Lindhout
Oct 9, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·T KlapecI Strelec
Oct 21, 2016·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Page B Pennell
Oct 21, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Valentina M FokinaTatiana N Nanovskaya
May 29, 2008·Expert Review of Neurotherapeutics·Svein I Johannessen, Cecilie Johannessen Landmark
Dec 22, 2009·Expert Review of Neurotherapeutics·Cecilie Johannessen Landmark, Philip N Patsalos
Mar 19, 2020·Pharmacogenetics and Genomics·Taraswi Mitra-GhoshRuss B Altman
Apr 16, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ming-Lu WangLimei Zhao
May 18, 2021·Frontiers in Pharmacology·Raju KhatriCraig R Lee
Nov 6, 2021·Expert Opinion on Drug Metabolism & Toxicology·Ian R MulreninCraig R Lee

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