Pharmacokinetics of gabapentin during delivery, in the neonatal period, and lactation: does a fetal accumulation occur during pregnancy?
OBJECTIVE
To study the pharmacokinetics of gabapentin (GBP) during delivery, lactation, and in the neonatal period.


METHODS
GBP concentrations in plasma and breast milk were determined with high-performance liquid chromatography in samples from six women treated with GBP and in their offspring. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from the newborns on three occasions during 2 days after delivery. GBP concentration also was determined in breast milk and in blood collected from five of the mothers and suckling infants 2 weeks to 3 months after birth.


RESULTS
The umbilical cord/maternal plasma concentration ratios ranged from 1.3 to 2.1 (mean, 1.7). GBP plasma concentrations in the neonates declined with an estimated half-life of 14 h. Mean GBP plasma concentrations in the infants were 27% of the cord plasma levels (range, 12-36%) 24 h postpartum. The mean milk/maternal plasma concentration ratio was 1.0 (range, 0.7-1.3) from 2 weeks to 3 months. The infant dose of GBP was estimated to 0.2-1.3 mg/kg/day, equivalent to 1.3-3.8% of the weight-normalized dose received by the mother. The plasma concentrations in the breast-fed infants were approximately 12% of the mother's plasma levels, but no adverse effects were observed.


CONCLUSIONS
Our limited observations suggest an active transplacental transport of GBP, with accumulation in the fetus as a consequence. We suggest that this could be by the specific L-type amino acid transporter 1 (LAT-1), which is expressed in the placenta. Newborns seem to have a slightly lower capacity to eliminate GBP than do adults. Transfer of GBP to breast milk is extensive, but plasma concentrations appear to be low in suckling infants. No adverse effects were observed in the newborn. Although more data are needed, our observations suggest that breastfeeding in conjunction with GBP treatment is safe.
Ohman
Inger
I
Department of Internal Medicine, Division of Clinical Pharmacology, Karolinska Institute at Karolinska University Hospital, Stockholm, Sweden. inger.ohman@medks.ki.se
Vitols
Sigurd
S
Tomson
Torbjörn
T
D000588:Amines / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000927:Anticonvulsants / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001942:Breast Feeding / Q000706:statistics & numerical data*; D003509:Cyclohexanecarboxylic Acids / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D000077206:Gabapentin; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn / Q000097:blood* / Q000378:metabolism; D007774:Lactation / Q000187:drug effects / Q000378:metabolism*; D027283:Large Neutral Amino Acid-Transporter 1 / Q000187:drug effects / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008895:Milk, Human / Q000737:chemistry / Q000378:metabolism; D036801:Parturition / Q000187:drug effects / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D049590:Postpartum Period / Q000097:blood / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D027283:Large Neutral Amino Acid-Transporter 1; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin