Effects of lacosamide "a novel antiepileptic drug" in the early stages of chicken embryo development

Childs Nerv Syst. 2016 Sep;32(9):1715-9. doi: 10.1007/s00381-016-3181-4. Epub 2016 Jul 29.

Abstract

Introduction: Antiepileptic drugs (AEDs) are teratogens and confer a risk of congenital malformation. The estimated prevalence of major congenital malformations such as cardiac defects, facial clefts, hypospadias, and neural tube defects in epileptic women is 4-10 %, which represents a two- to fourfold increase in pregnant women compared to the general population. However, there are no clear data for newer drugs. Lacosamide (LCM), a novel AED, is the first of the third-generation AEDs to be approved as adjunctive therapy for the treatment of partial-onset seizures. There are no data on the pharmacokinetics of LCM during pregnancy, and only some published data have reported on its effects during pregnancy.

Methods: In this study, three different doses of LCM (0.12, 0.5, and 1.60 mg in 0.18 mL) were applied under the embryonic disks of specific pathogen-free Leghorn chicken embryos after a 30-h incubation. Incubation was continued for 80 h, at which time all embryos were evaluated macroscopically and microscopically.

Results: There was growth retardation in all of the LCM-treated groups. Major malformations increased in a dose-dependent manner and were mostly observed in the supratherapeutic group.

Conclusion: Based on our data, LCM may cause growth retardation or major congenital malformations. Nevertheless, more extensive investigations of its reliability are needed.

Keywords: Anti-epileptic; Chick embryo; Lacosamide; Malformation.

MeSH terms

  • Acetamides / toxicity*
  • Animals
  • Anticonvulsants / toxicity*
  • Chick Embryo
  • Dose-Response Relationship, Drug
  • Embryonic Development / drug effects*
  • Embryonic Development / physiology
  • Female
  • Fetal Growth Retardation / chemically induced*
  • Fetal Growth Retardation / diagnosis*
  • Lacosamide
  • Nervous System Malformations / chemically induced
  • Nervous System Malformations / diagnosis
  • Pregnancy

Substances

  • Acetamides
  • Anticonvulsants
  • Lacosamide