title: Preclinical toxicology of zidovudine. An overview.
abstract: The toxicologic potential of zidovudine (azidothymidine) has been extensively investigated in several species. In rats and mice, the median lethal dose was greater than 750 mg/kg intravenously and greater than 3,000 mg/kg orally. In subacute intravenous toxicity studies, no significant toxicologic alterations were seen in rats or dogs. In cynomolgus monkeys, which as in humans rapidly and extensively glucuronidate zidovudine, a reversible, dose-related, macrocytic anemia was seen in animals given 35, 100, or 300 mg/kg per day for three or six months. In three-month and six-month oral toxicity studies in rats, treatment-related alterations consisted of a mild increase in glucose level in the blood in female rats in both studies and a reversible, slight-to-mild macrocytic anemia in the six-month study. There was no evidence of teratogenicity in rats or rabbits given the drug during gestation. Results for zidovudine were negative in a bacterial mutagenicity assay, but the drug was weakly mutagenic at concentrations of 1,000 to 5,000 micrograms/ml in mammalian cells. Zidovudine caused chromosomal aberrations in cultured human lymphocytes at concentrations of 3 micrograms/ml and higher and had positive results in a cell transformation assay at concentrations of 0.5 micrograms/ml and higher. No bone marrow chromosomal alterations were noted in a cytogenetics study in rats given zidovudine at several intravenous dose levels up to 300 mg/kg.
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D013936:Thymidine / Q000031:analogs & derivatives* / Q000633:toxicity; D015215:Zidovudine
chemical_list: D000998:Antiviral Agents; D015215:Zidovudine; D013936:Thymidine