Title : Study of the possible teratogenicity of daclatasvir on the pregnant mice
Abstract:
Congenital birth defects occur in about 5% of all live births. Drugs may account up to 1% of the known causes of birth defects. Hepatitis C virus (HCV) infection is a worldwide health problem. Its prevalence in pregnancy is between 1% and 8% of cases. Daclatasvir (DCV) is one of the second generation of the directly acting antiviral daclatasvir (DAAs). The FDA approval for daclatasvir has just been received for marketing in the U.S in 2016. Till now, it has not been included in a certain Pregnancy Category. Aim of the work was to explore the possible teratogenic effects of daclatasvir administration on fetuses of the pregnant mice. Forty pregnant mice were divided into two main groups; Group I (control group), included 10 mice which received distilled water. Group II (DCV group): included 30 mice subdivided into three equal groups: group IIa (DCV 12.5 mg/kg), group IIb (DCV 25 mg/kg) and group IIc (DCV 50 mg/kg). They received the drug orally from GD6 to GD15. The pregnant mice were sacrificed (at GD 18-19). All of the live fetuses were examined cranio-caudally for external malformations and processed for skeletal examination. Maternal toxicity in the form of decrease in maternal body weight gain and increased maternal mortalities were observed in DCV treated groups. A dose dependent increase in rate of fetal resorptions (early and late), decrease fetal body weight. A group of external anomalies were encountered in the form of; hyper-extension of forelimb, internal rotation of forelimb and hind limb, subcutaneous and incomplete ossification of parts of the skeleton (skull, vertebral column, ribs, sternum, forelimbs, and hindlimb). In conclusion, DCV administration during pregnancy has a potential risk of DILI. Future studies are recommended to improve maternal outcome.
