Neocarzinostatin (NSC-157 365, Kayaku Lot 720150):Preclinical Pharmacological Evaluation of Treatment With a Single Dose iv in Dogs.

摘要

Neocarzinostatin (NSC-157 365) Kayaku (K) lot 720150,an antibiotic from Streptomyces carzinostaticus var. F-41,was injected as a single dose iv in dogs. Treatment with 10to 0.31mg/kg produced dose related intestinal toxicity, hypocellularity of bone marrow and lymphoid tissues and death,primarily from intestinal toxicity,within 1to 10days. Tonsillitis and hemorrhagic pneumonia contributed to severe morbidity in dogs that died later than 1week after treatment. Dogs treated with 0.156mg/kg to 0.039mg/kg survived acute toxicity,however, 50% of them developed uremia and died 50to 116days after treatment from chronic interstitial nephritis, Myicarditis and myocardial infarctions also occurred and indicated a possible immunogenic pathogenesis for Neocarzinostatin K lesions though no precipitating antibodies were detectable. A single dose of 0.01mg/kg was nontoxic.