Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation.
OBJECTIVE
To investigate the pharmacokinetics of lamotrigine (LTG) during delivery, during the neonatal period, and lactation.


METHODS
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.


RESULTS
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%.


CONCLUSIONS
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.
Ohman
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Departments of Clinical Pharmacology and *Clinical Neuroscience, Section of Neurology, Karolinska Institute at Karolinska Hospital, Stockholm, Sweden. inoeh@mb.ks.se
Vitols
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Tomson
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D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001942:Breast Feeding; D002851:Chromatography, High Pressure Liquid; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn / Q000097:blood* / Q000378:metabolism; D000077213:Lamotrigine; D008895:Milk, Human / Q000737:chemistry* / Q000378:metabolism; D007744:Obstetric Labor Complications / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D011644:Puerperal Disorders / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D014227:Triazines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine