XXXX Causes Stage-Dependent Embryolethality in @entity3392 and Mouse In Vitro.

@entity1 @entity71301 @entity3753 @entity37472 @entity9158 @entity31867 @entity9643 @entity2439 @entity4801 @entity7736 @entity3392
BACKGROUND: @entity7736 and @entity9643 are widespread foodborne @entity2439 , affecting millions of @entity1 in more than 75 countries. The treatment of choice for these @entity4801 is based on @entity31867 , a @entity9158 derivative which has been suggested as a promising drug to treat pregnant @entity1 and @entity1 . However, at the moment, this drug is not approved for @entity1 use in most countries. Its potential adverse effects on embryonic development have been scarcely studied, and it has not been assigned a pregnancy category by the FDA. Thus, to help in the process of risk-benefit decision making upon @entity31867 treatment during pregnancy, a better characterization of its risks during gestation is needed. METHODOLOGY: The @entity3392 embryo test, a preimplantation and a postimplantation rodent whole embryo culture were used to investigate the potential embryotoxicity/teratogenicity of @entity31867 and its first metabolite @entity71301 . @entity3753 and @entity37472 were included as positive controls. PRINCIPAL FINDINGS: @entity31867 was between 10 and 250 times less potent than @entity3753 in inducing dysmorphogenic effects in @entity3392 or postimplantation rodent embryos, respectively. However, during the preimplantation period, both compounds, @entity31867 and @entity71301 , induced a dose-dependent embryolethal effect after only 24 h of exposure in rodent embryos and @entity3392 (lowest observed adverse effect concentrations = 10  M). CONCLUSIONS/SIGNIFICANCE: In @entity1 , after ingestion of the recommended doses of @entity31867 to treat @entity7736 and @entity9643 (10 mg/kg), the main compound found in plasma is @entity71301 (maximum concentration 38.6  M), while @entity31867 concentrations are approximately 30 times lower (1.16  M). From our results it can be concluded that @entity31867 , at concentrations of the same order of magnitude as the clinically relevant ones, does not entail teratogenic potential in vitro during the organogenesis period, but its first metabolite @entity71301 has a high embryotoxic capacity in vitro during the preimplantation stage.
