In vivo preliminary investigations of the effects of the benzimidazole anthelmintic drug flubendazole on rat embryos and fetuses

- Flubendazole-ASD is highly bioavailable and it is active as macrofilaricide.
- Embryotoxicity of flubendazole-ASD is evaluated after oral maternal treatment on GD 9.5 and 10.5.
- Flubendazole-ASD is embryolethal at 6.32 mg/kg/day (Cmax = 0.801 μg/mL).
- Flubendazole-ASD is teratogenic at 3.46 mg/kg/day (Cmax = 0.539 μg/mL).

Flubendazole, in a new formulation with high systemic bioavailability, has been proposed as a macrofilaricide against filarial diseases.To investigate embryotoxic activity, the new flubendazole formulation was administered orally to Sprague Dawley rats at 2, 3.46, 6.32 mg/kg/day on gestation day (GD) 9.5 and 10.5. Embryos/fetuses were evaluated on GD 11.5, 12.5 or 20.At 6.32 mg/kg/day (Cmax = 0.801 μg/mL after single administration), flubendazole initially induced an arrest of embryonic development followed by a generalized cell death that led to 100% embryolethality by GD 12.5.At 3.46 mg/kg/day (Cmax = 0.539 μg/mL after single administration), flubendazole markedly reduced embryonic development by GD 12.5 without causing cell death. On GD 20, 80% of fetuses showed malformations.At 2 mg/kg/day (Cmax = 0.389 μg/mL after single administration), it did not interfere with rat embryofetal development.