Repeated Intravenous Administration of Cytosine Arabinoside Triacetate to Beagle Dogs

摘要

Two beagle dogs, one male and one female, received daily intravenous doses of 50 mg/kg of cytosine arabinoside triacetate for 15 consecutive days. The surviving dog was observed for a period of 30 days following the 15-day dose regime. The criteria of effect evaluated were appearance and behavior, appetite and elimination, hematologic and biochemical values, and gross and microscopic pathology. Administration of cytosine arabinoside triacetate at a level of 50 mg/kg/day for 15 days produced an effect in both dogs, as evidenced by appearance, behavior, and survival, and from the results of clinical laboratory studies and microscopic pathology. Depression, elevation of body temperature, vomiting and/or diarrhea, and weight loss were observed immediately following completion of the 15-day dose regime. The male dog died four days following completion of administration. The results of hemograms of both dogs indicated decreases in cell volume and hemoglobin, and marked decreases in platelet and white blood cell counts. Both dogs showed elevated alkaline phosphatase values. The female dog that survived, was held for a 30-day observation period. During this interval the animal showed no adverse effects, ate well, and gained weight. Clinical laboratory values returned to normal. The results of the gross and microscopic pathologic evaluation indicated 50 mg/kg/day of cytosine arabinoside triacetate produced severe bone marrow suppression in both dogs with evidence of recovery of the marrow in the one dog that survived. (Author)