Methyl CCNU(NSC-95 441): Toxicity of a Single I.V. Infusion in Dogs. Vehicle 20% Absolute Alcohol-80% Propylene Glycol.

摘要

Methyl - CCNU on antineoplastic agent was submitted to a preclinical pharmacological evaluation in 10sex paired dogs. Single doses of 14, 9.37, 6.25, 3.12and 1.56mg/kg were intravenously infused in 20% ethanol - 80% propylene glycol over a period of 2to 29minutes. The concentration of the formulation was 35.7mg/ml. Irreversible clinical, hematological and pathological changes occurred only in the 2dogs treated with 14mg/kg which became moribund on days 9and 10. Severe hematopoietic toxicity manifested by leukopenia, neutropenia, lymphopenia,severe bone marrow hypoplasia and lymphoid atrophy lead to bacteremia,with necrotizing tonsillitis,focal fibrino -hemorrhagic pneumonia,acute phlebitis at injection sites and cardiac valvulitis. Dogs on lower doses survived and showed no gross or histopathological changes at the necropsy on days 49to 59.