Pharmacokinetics of Levetiracetam during Pregnancy, Delivery, in the Neonatal Period, and Lactation

• Published in: Epilepsia (Copenhagen) Vol. 48; no. 6; pp. 1111 - 1116
• Main Authors: Tomson, Torbjörn, Palm, Ragnar, Källén, Kristina, Ben‐Menachem, Elinor, Söderfeldt, Birgitta, Danielsson, Bo, Johansson, Rune, Luef, Gerhard, Öhman, Inger
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.06.2007; Blackwell
• Subjects: Anticonvulsants - analysis; Anticonvulsants - pharmacokinetics; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; birth; Breast Feeding - adverse effects; Breast milk; Clinical Medicine; Delivery, Obstetric - statistics & numerical data; Delivery. Postpartum. Lactation; Epilepsy; Epilepsy - blood; Epilepsy - drug therapy; Epilepsy - metabolism; Female; Fetal Blood - chemistry; Gynecology. Andrology. Obstetrics; Half-Life; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Infant, Newborn - blood; Infant, Newborn - metabolism; Klinisk medicin; Lactation - blood; Lactation - metabolism; Levetiracetam; Maternal-Fetal Exchange - drug effects; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Milk, Human - chemistry; Milk, Human - metabolism; Nervous system (semeiology, syndromes); Neurologi; Neurology; Neuropharmacology; Pharmacokinetics; Pharmacology. Drug treatments; Piracetam - analogs & derivatives; Piracetam - analysis; Piracetam - pharmacokinetics; Piracetam - therapeutic use; Pregnancy; Pregnancy Complications - blood; Pregnancy Complications - drug therapy; Pregnancy Complications - metabolism; Pregnancy Trimester, Third - blood; Pregnancy Trimester, Third - metabolism; Prospective Studies; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Puerperal Disorders - blood; Puerperal Disorders - drug therapy; Puerperal Disorders - metabolism; Human; Epilepsy- Pregnancy-Levetiracetam-Pharmacokinetics-Breast milk; Nervous system diseases; Lactation; Psychotropic; Epilepsy; Anticonvulsant; Cerebral disorder; Pregnancy; Newborn; Nootropic agent; Central nervous system disease; Delivery; Pharmacokinetics; Breast milk; Levetiracetam
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2007.01032.x

Purpose: 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.