Abstracts

Rationale: Lamotrigine (LTG) has become an increasingly popular antiepileptic drug (AED) for the treatment of women with epilepsy of childbearing age. However, relatively few reports of LTG concentration in exposed neonates and breast milk are available. The aim of this study was to measure neonatal pharmacokinetics and breast milk penetration of LTG. Methods: Pregnant women with epilepsy on LTG were invited to participate. Total LTG concentrations were determined at delivery in maternal plasma and umbilical cord blood and in maternal and infant plasma at 24, 48, and 72 hours (if the patient is still hospitalized) post delivery. In mothers electing to breastfeed, plasma and breast milk LTG concentrations were determined 1 week and 3 months post partum as were LTG plasma concentrations in infants. In mothers not breastfeeding, plasma LTG concentrations were determined at the same intervals and infant LTG concentrations were determined 1 week post birth only. Dose adjustments were made to manage seizures and adverse effects in mothers. Neonatal concentration/maternal concentration was determined at each interval including on the cord blood sample (placental transfer). Breast milk penetration (milk/maternal concentration), breast feeding ratio (nursing neonate concentration/maternal concentration) and relative infant dose (RID; dose infant/dose maternal x 100) were calculated. Results: Eleven mother-infant pairs participated and 5 infants were breastfed. Fifty-two maternal, 39 neonatal and 7 breast milk samples were obtained. Data are presented as mean (+ SD). Placental transfer was 0.980 (0.091). Neonatal concentration/maternal concentration was 0.713 (0.184) at 24 hours, 0.709 (0.440) at 48 hours and 0.288 (0.039) at 72 hours post delivery. Breast milk penetration was 0.526 (0.212) overall. Breast feeding ratio was 0.550 (0.387). Median RID (IQR) for all infants over the study period was 0.787 (0.509 - 2.122), for breastfed infants 2.073 (0.641 - 2.439), and for non breast feeding infants 0.544 (0.421 - 1.579). No adverse effects were observed in the infants. Conclusions: Our findings confirm and extend prior observations indicating that while marked placenta transfer of LTG occurs in exposed infants, no significant accumulation is observed after birth. Breast milk penetration is comparable to previous reports and not greater than that observed with other AEDs. Supported by a grant from GlaxoSmithKline.