Abstracts

The treatment of women with epilepsy during pregnancy necessitates a balance between minimizing fetal exposure to AEDs while maintaining seizure control. Oxcarbazepine (OXC) is the only newer generation AED other than lamotrigine (LTG) with reasonable safety data during pregnancy. Reports of major malformation rates vary between 0-5%. However, EURAPregnancy Registry reported that use of OXC monotherapy was associated with an increased risk for GTCSzs, and the number or dosage of AEDs were most often increased in pregnancies treated with OXC or LTG monotherapy. This observational study did not report on serum concentrations or OXC clearance. About 50% of the metabolism of the 10-monohydroxy derivative (MHD) of OXC is via glucuronidation, which is especially susceptible to activation by the hormonal changes of pregnancy., 5 women (4 epilepsy, 1 bipolar disorder) treated with OXC (doses of 450-3000 mg/day) were consented and followed in a prospective observational study. Serum samples were obtained throughout pregnancy and until 5 months postpartum (n=27). Postpartum samples were considered the non-pregnant baseline. Maternal plasma and umbilical cord samples were also collected at delivery (n=4). Comparisons of the total apparent oral clearance(Cl/F) and free (unbound) apparent oral clearance (Clu/F) were made between the postpartum (baseline) and perinatal stages. Umbilical cord/maternal concentration ratios were calculated for total and free MHD., Cl/F and Clu/F data from the postpartum and perinatal stages are reported in Table 1. Umbilical cord/maternal concentrations demonstrated a mean placental passage of 1.0[plusmn]0.3 (total) and 1.1[plusmn]0.2 (free) for MHD. Obstetrical outcome demonstrated mean APGAR scores of 8.5[plusmn]0.6 at 1 min, 9.0[plusmn]0.0 at 5 mins, birth weights of 3.2[plusmn]0.4 kg, and weeks at delivery of 39.4[plusmn]1.0. No major malformations were detected., During pregnancy, both total MHD Cl/F and free MHD Cl/F increase considerably, although the latter to a lesser degree. Substantial exposure occurs in utero with complete placental passage of OXC. Therapeutic drug monitoring of OXC may be helpful to prevent seizure deterioration during pregnancy and improve maternal and fetal outcomes.[table1], (Supported by a Specialized Center for Research P50 MH 68036.)