Individual changes in lamotrigine plasma concentrations during pregnancy

Department of Clinical Neurophysiology 3063, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Epilepsy Research (Impact Factor: 2.02). 08/2005; 65(3):185-8. DOI: 10.1016/j.eplepsyres.2005.06.004
Source: PubMed


Eleven pregnant women on lamotrigine (LTG) monotherapy were retrospectively reviewed. A significant decrease in the ratio of plasma LTG concentration-to-dose by 65.1% was observed during the second trimester (TM2) (p=0.0058) and by 65.8% during TM3 (p=0.0045) compared to pre-pregnancy values. Five patients experienced seizure deterioration during pregnancy. The pharmacokinetic changes display marked inter-patient variation, which stresses the importance of evaluating each woman individually by closely monitoring LTG concentrations until term.

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Available from: Vaiva Petrenaite, Feb 12, 2015
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    • "LTG serum concentrations fall by over 50% during pregnancy, most presumably due to increased glucuronidation (de Haan et al. 2004; Ohman et al. 2008, 2000; Pennell et al. 2004; Petrenaite et al. 2005). This may lead to loss of seizure control and the necessity to increase the LTG dose (Petrenaite et al. 2005). It is unlikely that pregnancy-induced hemodilution plays a major role in this "
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    ABSTRACT: The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50% during pregnancy, leading to impaired seizure control. The placenta may be involved in this. Microsomes from term placentas of 4 LTG-users and 10 healthy control subjects were prepared. Western blot analysis detected UGT1A proteins in all placentas. The presence of UGT1A4 in placenta from LTG users was confirmed with UGT1A4 commercial standard and a specific UGT1A4 primary antibody. Since LTG is primarily metabolized by UGT1A4 and this isozyme is shown to be present in placenta at term, it may be hypothesized that the placenta is involved in the fall of LTG serum concentrations during pregnancy.
    European Journal of Drug Metabolism and Pharmacokinetics 01/2011; 35(3-4):79-82. DOI:10.1007/s13318-010-0021-x · 1.56 Impact Factor
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    • "A. Sabers and V. Petrenaite at the beginning of the second trimester, this means that most of the women in this study population had been monitored in the clinic at least once every month after the pregnancy had been realized. The LTG doses had been adjusted three to four times for the individual patient in this study population, representing thereby a monitoring frequency that is almost double that of our previous report (Petrenaite et al., 2005). However, the fact that seizure deterioration was less frequent compared to other studies may also reflect better compliance with treatment regimens when the patients know their LTG levels are monitored and when they have close personal contact with a specific physician throughout pregnancy. "
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    ABSTRACT: Previous studies have demonstrated that the pharmacokinetics of the new antiepileptic drug (AED) lamotrigine (LTG) are substantially influenced by pregnancy and are more likely to be associated with seizure deterioration in pregnancy compared to other AEDs. This is of great concern, as LTG has developed into a first-line AED for women of childbearing age. In this study we evaluated the risk of seizure deterioration in a cohort of women treated with LTG monotherapy (n = 42) who were closely monitored with frequent dose adjustments based on monthly routine plasma level determinations. It was demonstrated that with this close monitoring set-up, the risk of increased seizure frequency (19%) was not higher than that reported for other AED treatment regimens.
    Epilepsia 07/2009; 50(9):2163-6. DOI:10.1111/j.1528-1167.2009.02166.x · 4.57 Impact Factor
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    • "This elimination pathway appears particularly susceptible to activation during pregnancy, most likely as a result of direct effects of rising sex steroid hormone levels. An early retrospective study reported an approximately 150% increase in LTG clearance in the second and third trimesters of pregnancy (n = 11) (Petrenaite et al., 2005), 49 Safety "
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    ABSTRACT: Most infants born to women with epilepsy are healthy, but there are increased risks related to in utero antiepileptic drug (AED) exposure and seizures. Emerging data from pregnancy registries and other studies allow us to better balance the anatomic teratogenic and neurodevelopmental effects of AEDs against the need to maintain maternal seizure control. Several large prospective pregnancy registries demonstrate a consistent pattern of increased risk for major congenital malformations (MCMs) with valproate (VPA) use as monotherapy, compared to nonexposed populations and to other AEDs used in monotherapy. AED polytherapy likely increases risk for MCMs, but the risk is more pronounced if VPA is included. Reduced cognitive outcomes have been reported with AED polytherapy, and with use of VPA, phenobarbital (PB), and PHT as monotherapy. Dose-dependent risk has been demonstrated with VPA for MCMs and cognitive consequences. CBZ groups show normal neurodevelopment. Increased clearance of most of the AEDs occurs during pregnancy. Use of therapeutic drug monitoring during pregnancy with LTG reduces the risk for seizure worsening. The consistent findings of increased teratogenic risk for VPA should discourage use of this medication as first-line treatment in women of childbearing age.
    Epilepsia 01/2009; 49 Suppl 9(s9):43-55. DOI:10.1111/j.1528-1167.2008.01926.x · 4.57 Impact Factor
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