Lamotrigine kinetics within the menstrual cycle, after menopause, and with oral contraceptives.

OBJECTIVE: We prospectively evaluated the fluctuation of lamotrigine (LTG) clearance during the menstrual cycle. We also assessed the effect of postmenopausal status and investigated in detail the effect of oral contraceptives (OCs) on LTG clearance. METHODS: Three groups of women with epilepsy using LTG monotherapy were evaluated. Women in the first group (n = 7) had a regular cycle and did not use OCs; the second group used a 1-phase combined OC (n = 7), and the third group (n = 7) was postmenopausal. Two menstrual cycles or at least 2 months (postmenopausal women) were assessed, monitoring LTG levels every other day. RESULTS: The mean apparent LTG clearance in women of reproductive age not using OCs was 49 (SD 22.6, range 20.4-83.5) L/24 hours. No significant effect of endogenous hormones on LTG clearance was found. In women using OCs, the mean LTG clearance was 126 (SD 60.2, range 44.3-205) L/24 hours. There was an increase in LTG levels during the pill-free week, with maximum levels 54% (range 29%-129%) higher than baseline levels. LTG levels decreased to the baseline value within a mean of 8 days of starting OC use (SD 3.7, range 2.5-16.5). In the postmenopausal women, the mean clearance was 82 (SD 38.4, range 35.9-125) L/24 hours. CONCLUSIONS: We observed a higher mean lamotrigine (LTG) clearance in postmenopausal women compared with young women not using oral contraceptives (OCs) and confirmed that OC use may have a strong effect on LTG clearance. There was no significant fluctuation of LTG clearance during the menstrual cycle

Eritrea

Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel C 200008 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Aethiopien

Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel C 200012 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Association of Levetiracetam Concentration With Seizure Frequency in Pregnant Women With Epilepsy

BACKGROUND AND OBJECTIVES: Pharmacologic treatment of epilepsy in pregnant women is balancing between risks for mother and for fetus. Levetiracetam (LEV) is considered to be safe during pregnancy because of its low teratogenic potential and lack of drug-drug interaction with other anti-seizure medications (ASMs). Recent studies have shown decline of ASM concentrations during pregnancy because of physiologically-based pharmacokinetic changes. In this study, we established this decrease in LEV concentration during pregnancy. Additionally, we aimed at investigating the effect of the low LEV levels during pregnancy and develop a target value for the level during pregnancy. METHODS: Pregnant patients using levetiracetam were studied in this retrospective cohort study. Blood samples were monthly collected through venous puncture or the dried blood spot method. ASM serum concentrations were determined at least six months prior to conception and for each month of pregnancy. Seizure frequency and ASM dosages during pregnancy were obtained from patient records. Patients were divided into two groups: a 'seizure free' and a 'non-seizure free' group which contained pregnancies in which mother had experienced an epileptic seizure more than twelve months and less than twelve months before pregnancy, respectively. RESULTS: We found decreased concentration/dose ratios in 29 pregnancies throughout all months of pregnancy. In the non-seizure free group, it was found that low LEV concentrations were associated with seizure increase frequency (p=0.022). For this group the cut off-value with the highest sum of sensitivity and specificity was 0.466. DISCUSSION: All in all, we recommend therapeutic drug monitoring for all pregnant patients on LEV as the concentrations of LEV significantly decrease throughout most months of pregnancy. However, this decrease in LEV concentration was only significantly correlated with seizure deterioration in patients who had a seizure in the year preceding the pregnancy . Therefore, we suggest more careful monitoring of non-seizure free patients as they are at higher risk for experiencing an increase of seizure frequency. For this group, we advise physicians to keep LEV concentration above 65% of the preconceptional concentration. For seizure free patients we recommend a LEV threshold value of approximately 46% of the preconceptional concentration