Comparison of the neonatal toxicity of two antiviral agents: Vidarabine phosphate and cytarabine

Abstract

Two-day-old rats were administered daily ip injections of either vidarabine phosphate (VP) at nonlethal dose levels of 400, 200, 100, and 25 mg/kg or cytarabine (cytosine arabinoside, ara-C) at 4 mg/kg for 5 consecutive days and then observed for 28 days. Age-matched rats were injected with the vehicle or untreated and served as controls. One male and one female rat per group were necropsied at 5, 12, 19, and 33 days for pathologic evaluation of organogenesis. VP at 400, 200, and 100 mg/kg induced retarded hair growth around the injection site at 12 days which was resolved completely by 19 days. No other significant pathologic or developmental changes were noted with VP in neonatal rats. With ara-C significant weight gain suppression, delayed hair growth, and unsteady gait were evident during the observation period. Retarded development of the dermis, cerebellar hypoplasia, retinal dysplasia, and delayed nephrogenesis appeared at 12 days and were the principal pathologic findings associated with ara-C treatment. Cerebellar and ocular changes persisted to study termination while pathologic findings in the dermis and kidney were not found at 33 days. Comparison of the neonatal toxicity of two antiviral agents revealed that VP treated rats presented focal dermal changes localized to the site of drug administration and no significant developmental anomalies in contrast with the systemic alterations induced by ara-C.