7/27/2019 Pharmacokinetics of Levetiracetam During Pregnancy, Delivery, In the Neonatal Period, And Lactation

1/6

Epilepsia, 48(6):11111116, 2007Blackwell Publishing, Inc.C 2007 International League Against Epilepsy

Pharmacokinetics of Levetiracetam during Pregnancy, Delivery,

in the Neonatal Period, and Lactation

Torbjorn Tomson, Ragnar Palm, Kristina Kallen, Elinor Ben-Menachem, Birgitta Soderfeldt,Bo Danielsson, Rune Johansson, Gerhard Luef, and IngerOhman

Departments ofClinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Neurologmottagning Ankaret, Karlstad, Sweden;Neurology, Lund University Hospital, Sweden; Clinical Neuroscience and Physiology, Sahlgrenska University Hospital, G oteborg,

Sweden; Internal Medicine, Stockholm South Hospital, Stockholm, Sweden; Neurology, M alarsjukhuset, Eskilstuna, Sweden;Neurology and Rehabilitation, Central Hospital, Karlstad, Sweden; Neurology, University Hospital Innsbruck, Austria;

Internal Medicine, Division of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden

Summary: Purpose: To study pharmacokinetics of levetirac-etam (LEV) during pregnancy, delivery, lactation, and in theneonatal period.

Methods: Fourteen women with epilepsy receiving LEVtreat-ment during pregnancy and lactation contributed with 15 preg-nancies to this prospective study in which LEV concentrationsin plasma and breast milk were determined. Trough maternalplasma samples were collected each trimester, and at baselineafter delivery. Blood samples were obtained at delivery frommothers, from the umbilical cord, and from newborns during 2days after delivery. LEV concentration was also determined inbreast milk and in plasma collected from 11 of the mothers andtheir suckling infants after birth.

Results: The umbilical cord/maternal plasma concentrationratios ranged from 0.562.0 (mean 1.15, n = 13). LEV plasmaconcentrations in the neonates declined with an estimated half-

lifeof 18h (n= 13). The mean milk/maternal plasma concentra-tion ratio was 1.05 (range, 0.781.55, n = 11). The infant doseof LEV was estimated to 2.4 mg/kg/day, equivalent to 7.9% ofthe weight-normalized maternal dose. Plasma concentrations inbreastfed were approximately 13% of the mothers plasma lev-els. Maternal plasma concentrations during third trimester wereonly 40% of baseline concentrations outside pregnancy (p