Repeated Intravenous Administration of Methotrexate to Rhesus Monkeys

摘要

Methotrexate (MTX) was administered intravenously to male rhesus monkeys in twice weekly doses of 5.0, 6.0 and 7.0 mg/kg. Aqueous solution of Methotrexate was prepared with the use of IN NaOH at a concentration of 25 mg/ml. The criteria of effect evaluated were appearance, behavior, appetite, weight gain, hematologic and biochemical studies and gross and microscopic pathology. Methotrexate administered intravenously twice a week produced weakness, decreased appetite, weight loss, soft stools or diarrhea, and death in three of four monkeys. The first animal died on Day 24 following seven doses of 5.0 mg/kg. The second animal died on Day 32 following four doses at 5.0 mg/kg, four doses at 6.0 mg/kg and one dose at 7.0 mg/kg. The third animal died on Day 90 having received 10 doses of 5.0 mg/kg, four doses at 6.0 mg/kg and 12 doses at 7.0 mg/kg. The fourth animal was sacrificed on Day 45 having received 10 doses at 5.0 mg/kg. Methotrexate caused depression of white cell count in two of the four monkeys prior to death. Hematocrit and red blood cell counts remained fairly stable. Blood urea nitrogen and serum transaminase values were elevated prior to death in two of the animals. Pathologic changes were found in the intestines, kidneys and bone marrow. (Author)