Ohman I, Vitols S, Tomson T
Departments of Clinical Pharmacology and *Clinical Neuroscience, Section of Neurology, Karolinska Institute at Karolinska Hospital, Stockholm, Sweden.
Epilepsia. 2000 Jun;41(6):709-13. doi: 10.1111/j.1528-1157.2000.tb00232.x.
To investigate the pharmacokinetics of lamotrigine (LTG) during delivery, during the neonatal period, and lactation.
High-performance liquid chromatography was used to determine plasma and milk levels of LTG in nine pregnant women with epilepsy treated with LTG, and plasma levels in their 10 infants. Samples were obtained at delivery, the first 3 days postpartum, and at breast-feeding 2-3 weeks after delivery.
At delivery, maternal plasma LTG concentrations were similar to those from the umbilical cord, indicating extensive placental transfer of LTG. There was a slow decline in the LTG plasma concentration in the newborn. At 72 h postpartum, median LTG plasma levels in the infants were 75% of the cord plasma levels (range, 50-100%). The median milk/maternal plasma concentration ratio was 0.61 (range, 0.47-0.77) 2-3 weeks after delivery, and the nursed infants maintained LTG plasma concentrations of approximately 30% (median, range 23-50%) of the mother's plasma levels. Maternal plasma LTG concentrations increased significantly during the first 2 weeks after parturition, the median increase in plasma concentration/dose ratio being 170%.
Our data demonstrate a marked change in maternal LTG kinetics after delivery, possibly reflecting a normalization of an induced metabolism of LTG during pregnancy. LTG is excreted in considerable amounts in breast milk (the dose to the infant can be estimated to >/=0.2-1 mg/kg/day 2-3 weeks postpartum), which in combination with a slow elimination in the infants, may result in LTG plasma concentrations comparable to what is reported during active LTG therapy. No adverse effects were observed in the infants, however.
研究拉莫三嗪（LTG）在分娩期、新生儿期及哺乳期的药代动力学。
采用高效液相色谱法测定9例接受LTG治疗的癫痫孕妇血浆及乳汁中LTG水平，以及她们10例婴儿的血浆水平。在分娩时、产后前3天及分娩后2 - 3周母乳喂养时采集样本。
分娩时，母体血浆LTG浓度与脐带血相似，表明LTG可通过胎盘大量转运。新生儿血浆中LTG浓度下降缓慢。产后72小时，婴儿血浆中LTG水平中位数为脐血血浆水平的75%（范围50 - 100%）。分娩后2 - 3周，乳汁/母体血浆浓度中位数比值为0.61（范围0.47 - 0.77），哺乳婴儿维持的LTG血浆浓度约为母亲血浆水平的30%（中位数，范围23 - 50%）。产后前2周母体血浆LTG浓度显著升高，血浆浓度/剂量比值中位数升高170%。
我们的数据表明分娩后母体LTG药代动力学有显著变化，可能反映了孕期诱导的LTG代谢正常化。LTG在母乳中有大量排泄（产后2 - 3周婴儿摄入剂量估计≥0.2 - 1mg/kg/天），这与婴儿体内清除缓慢相结合，可能导致婴儿血浆LTG浓度与LTG积极治疗时报道的浓度相当。然而，未观察到婴儿有不良反应。
