Postnatal survival in Wistar rats following oral dosage with zidovudine on gestation day 10

Groups of 20 female Wistar rats from Charles River Breeding Laboratories (Kingston, NY) were given three oral doses of 100 mg zidovudine/kg at 5-hr intervals on Gestation Day 10 (total dose = 300 mg/kg). Control rats received three oral doses of the vehicle, distilled water. This design approximated that of an earlier study that reported 38% postnatal mortality among the offspring of Wistar rats given zidovudine. In the study reported here, no adverse effects were noted on maternal body weight, food consumption, reproductive capacity, or hematology. Similarly, no effects on growth or survival of the offspring were noted. Hematology and clinical chemistry values were comparable between offspring of treated and control dams, and no treatment-related gross or histopathologic lesions were noted in the weanling rats. The mean concentration of zidovudine in embryonal homogenates, collected 30 min after administration of the third dose to the dam on Gestation Day 10, was 21.1 micrograms/g tissue. This value is approximately one-third of the mean drug plasma concentration (62.6 micrograms/ml) measured in the dams at the same time point. The dramatic difference in results in the two studies may be related to differences in Wistar rats from two different sources or to other unknown factors associated with the design and conduct of the studies. The results of the current study were consistent with other preclinical studies on the reproductive toxicity of zidovudine in rats and rabbits.