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

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2016

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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. © 2016, Springer-Verlag Berlin Heidelberg.

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