Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation.
OBJECTIVE
To study pharmacokinetics of levetiracetam (LEV) during pregnancy, delivery, lactation, and in the neonatal period.


METHODS
Fourteen women with epilepsy receiving LEV treatment during pregnancy and lactation contributed with 15 pregnancies to this prospective study in which LEV concentrations in plasma and breast milk were determined. Trough maternal plasma samples were collected each trimester, and at baseline after delivery. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from newborns during 2 days after delivery. LEV concentration was also determined in breast milk and in plasma collected from 11 of the mothers and their suckling infants after birth.


RESULTS
The umbilical cord/maternal plasma concentration ratios ranged from 0.56-2.0 (mean 1.15, n=13). LEV plasma concentrations in the neonates declined with an estimated half-life of 18 h (n=13). The mean milk/maternal plasma concentration ratio was 1.05 (range, 0.78-1.55, n=11). The infant dose of LEV was estimated to 2.4 mg/kg/day, equivalent to 7.9% of the weight-normalized maternal dose. Plasma concentrations in breastfed were approximately 13% of the mother's plasma levels. Maternal plasma concentrations during third trimester were only 40% of baseline concentrations outside pregnancy (p<0.001, n=7)


CONCLUSIONS
Our observations suggest considerable transplacental transport of LEV and fairly slow elimination in the neonate. Plasma concentrations of LEV in nursed infants are low despite an extensive transfer of LEV into breast milk. Pregnancy appears to enhance the elimination of LEV resulting in marked decline in plasma concentration, which suggests that therapeutic monitoring may be of value.
Tomson
Torbjörn
T
Deparatment of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. torbjorn.tomson@karolinska.se
Palm
Ragnar
R
Källén
Kristina
K
Ben-Menachem
Elinor
E
Söderfeldt
Birgitta
B
Danielsson
Bo
B
Johansson
Rune
R
Luef
Gerhard
G
Ohman
Inger
I
D000927:Anticonvulsants / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001942:Breast Feeding / Q000009:adverse effects; D036861:Delivery, Obstetric / Q000706:statistics & numerical data; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn / Q000097:blood* / Q000378:metabolism; D007774:Lactation / Q000097:blood / Q000378:metabolism; D000077287:Levetiracetam; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D008895:Milk, Human / Q000737:chemistry / Q000378:metabolism; D010889:Piracetam / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D011263:Pregnancy Trimester, Third / Q000097:blood / Q000378:metabolism; D011446:Prospective Studies; D011644:Puerperal Disorders / Q000097:blood / Q000188:drug therapy / Q000378:metabolism
D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam