Fetal toxicity of benzodiazepines in rats

This study was undertaken to evaluate fetal toxicity of benzodiazepine derivatives, nitrazepam, oxazepam, nimetazepam, clonazepam, diazepam and chlordiazepoxide. In fetotoxicities induced by the oral administration of these six drugs (100 mg/kg), nitrazepam (NTZ) and nimetazepam caused a great damage to the fetus compared with other analogues. The fetotoxicity of NTZ was dose-dependent at a dose of 50 to 100 mg/kg p.o. and its peak toxicity was observed in the group treated from the 8th to 10th day of gestation. Maternal serum and whole fetus concentration of NTZ were higher than that of diazepam which showed weak toxicity. It was suggested that the intensity of fetotoxicity induced by benzodiazepines was related to the amount of drug in blood of dam.