Comparative study on the teratogenicity of some antiepileptics in the rat
El-Sayed, M.G.; Aly, A.E.; Kadri, M.; Moustafa, A.M.
East African Medical Journal 60(6): 407-415
1983
ISSN/ISBN: 0012-835X PMID: 6673960 Document Number: 5120
Three commonly used entiepileptics i.e. carbamazepine, ethosuximide and phenytoin were chosen for investigation of their teratogenic effects in rats. The drugs were given orally in two dose levels, i.e. the therapeutic and double the therapeutic dose, on days 9 to 17 of pregnancy which covers the period of organogenesis. The rats were killed on the nineteenth day of pregnancy and the fetuses were examined macro- and -microscopically. The histopathological changes in the brain, kidneys, liver, uterus and placenta of the treated mothers were investigated. A decrease in the number of viable fetuses/mother, mean weight and length of foetuses as well as an increase in the number of resorbed and dead fetuses/mother were seen. The major defects such as incomplete ossification of the cranial hones, ribs, pelvic girdle, decrease in the number of ribs, absence of phalanges: hydrocephalus: cleft palate and coelomia were recorded. The statistical analysis of the results showed that phenytoin produced the highest incidence of major defects of teratogenicity. Ethosuximide produced a lower but still significant incidence of foetal malformations. The lowest incidence was produced by carhamazepine.
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