CCNU (NSC-79 037): Toxicity of One Single I.V. Infusion in Rhesus Monkeys (Vehicle: 80% Propylene Glycol, 20% Ethanol),

摘要

For preclinical pharmacological evaluation,groups of 2or 3monkeys were submitted to a 20minute I.V. infusion with 20, 10, 5or 2.5mg/kg/ CCNU (Urea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitroso- 14.28mg/ml in 20% ethanol, 80% propylene glycol). One of two monkeys treated with 1infusion of 20mg/kg developed acute hypocellularity of the bone marrow and lymphoid tissues and became moribund on day 22from renal toxicity. The other died on day 113from chronic interstitial nephritis,uremia and hypercalcemia. Monkeys treated with 10mg/kg or less,survived in good general condition and exhibited reversible neutropenia, lymphopenia,anemia,elevation of the serum transaminases,AP and occasionally BUN. Histopathologic lesions were restricted to animals treated with 10mg/kg and included nephritis (2/3) and hydropic changes of the liver (1/3). One I.V. infusion of 2.5mg/kg,was nontoxic. Renal toxicity was,therefore,the treatment limiting toxicity in monkeys incontrast with agranulocytosis and sepsis in dogs. In the monkeys,the lethal dose for CCNU was 2/3as great for Methyl CCNU (NSC-95 441). Both drugs showed the same toxicity pattern. (Author)