Topiramate kinetics during delivery, lactation, and in the neonate: preliminary observations.
OBJECTIVE
To study the pharmacokinetics of topiramate (TPM) during delivery, lactation, and in the neonate.


METHODS
TPM concentrations in plasma and breast milk were measured with fluorescence polarization immunoassay (FPIA) in five women with epilepsy treated with TPM during pregnancy and lactation. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from the newborns on three occasions (24, 48, and 72 h) after delivery. Blood and breast milk also were collected from mothers 2 weeks, and 1 and 3 months postpartum. Blood samples also were drawn from the infants during breast-feeding. Three of the mother-infant pairs were studied both at delivery and during lactation; two contributed with data from delivery only.


RESULTS
The umbilical cord plasma/maternal plasma ratios were close to unity, suggesting extensive transplacental transfer of TPM. The mean milk/maternal plasma concentration ratio was 0.86 (range, 0.67-1.1) at 2-3 weeks after delivery. The milk/maternal plasma concentration ratios at sampling 1 and 3 months after delivery were similar (0.86 and 0.69, respectively). Two to 3 weeks after delivery, two of the breast-fed infants had detectable (>0.9 microM) concentrations of TPM, although below the limit of quantification (2.8 microM), and one had an undetectable concentration.


CONCLUSIONS
Our limited data suggest free passage of TPM over the placenta and an extensive transfer into breast milk. Breast-fed infants had very low TPM concentrations, and no adverse effects were observed in the infants.
D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001942:Breast Feeding; D036861:Delivery, Obstetric; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000187:drug effects / Q000378:metabolism; D016231:Fluorescence Polarization Immunoassay; D005632:Fructose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D007774:Lactation / Q000187:drug effects / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D008895:Milk, Human / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000378:metabolism*; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose