Failure of epoxide formation to influence carbamazepine-induced teratogenesis in a mouse model

The teratogenic potential of the anticonvulsant drug carbamazepine was determined following chronic oral administration in two inbred mouse strains (SWR/J and LM/Bc). The drug was administered in the animal's diet in concentrations equivalent to 0, 1,000, 1,500, or 2,000 mg/kg body weight, with treatment starting 2 wks prior to mating and continuing throughout gestation. Fetal examination failed to reveal a significant pattern of malformation in either strain at any treatment level. Levels of plasma carbamazepine and its metabolite, carbamazepine-10,11-epoxide, were determined by high pressure liquid chromatography. There was no correlation with either of these compounds and the incidence of fetal abnormality. The inherent teratogenicity of carbamazepine is significantly lower than that of other anticonvulsant drugs that have been similarly tested in an animal model.