Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

UGT polymorphisms and lamotrigine clearance during pregnancy

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Pharmacodynamics of remifentanil. Induced intracranial spike activity in mesial temporal lobe epilepsy

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Maternal and fetal outcomes associated with vagus nerve stimulation during pregnancy

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Dynamics of muscle activation during tonic-clonic seizures

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Alternative diets to the classical ketogenic diet-Can we be more liberal?

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. No effect of oral contraceptives on the metabolism of levetiracetam

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Characterization of Familial and Sporadic Migraine

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Associations between electroencephalography power and Alzheimer's disease in persons with Down syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Psychogenic nonepileptic seizures treated with psychotherapy: Long-term outcome on seizures and healthcare utilization

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

OBJECTIVE: To evaluate the impact of maternal UGT1A4 and UGT2B7 genetic polymorphisms and sex of foetus on gestation-induced changes in lamotrigine (LTG) clearance during pregnancy and post-partum (PP).

METHODS: Single nucleotide polymorphisms UGT1A4 142T > G, L48V (*3), UGT1A4 70C > A, P24T (*2) and UGT2B7 802C > T, H268Y (*2) were determined in 40 women (47 pregnancies) with epilepsy treated with LTG. Retrospectively collected data included LTG dosage and LTG plasma levels before pregnancy (T0), and LTG dosage and LTG plasma level changes in the first (T1), second (T2) and third trimester (T3), and post-partum (PP) as well as the sex of the foetus.

RESULTS: Reductions in the LTG concentration-to-dose ratio (C/D ratio) during pregnancy were seen in all genotype panels and varied between -53% and -74% in T3. Genetic polymorphism of UGT1A4 T142G (*3) and UGT2B7 C802T (*2) had the most pronounced influence on LTG clearance. Women with UGT1A4 142TG had a lower decrease in the C/D ratio in T3 than those with wild type: -53% (95%CI: -68% to -39%) versus -65% (95%CI: -69% to -60%) (p = 0.04). In homozygous carriers of UGT2B7 802TT the LTG C/D ratio was reduced significantly already in T1 (p = 0.015) as well as in T3 compared to the heterozygous carriers (802CT) (p = 0.04). Multiple regression analysis demonstrated that women who carried a female foetus had a significantly higher reductions in the LTG C/D ratio from T0 to the end of pregnancy than those with a male foetus (p = 0.003). In the univariate analysis the reductions in LTG C/D ratio were -64% in T2 (95%CI: -69% to -59%) and -67% in T3 (95%CI: -71% to -63%) in women who expected a female child compared to whose with a male child -58% in T2 (p = 0.002, 95%CI: -67% to -48%) and -57% in T3 (p < 0.001, 95%CI: -65% to -48%).

CONCLUSION: Genetic polymorphism in UGT1A4 and UGT2B7 may play a modest role in LTG clearance changes during pregnancy. In addition, our study indicates that the sex of the foetus influenced significantly the change in LTG clearance.

Original languageEnglish
JournalEpilepsy Research
Volume140
Pages (from-to)199-208
ISSN0920-1211
DOIs
Publication statusPublished - 2018

    Research areas

  • Journal Article

ID: 52751712