Neocarzinostatin (NSC-69 856,Bristol Lot 71L 1052): Preclinical Pharmacological Evaluation in Dogs.

摘要

I. V. injection with a single large dose of 20mg/kg led to acute toxicity,and death occurred on day 4from intestinal toxicity. Three doses of 5mg/kg injected at weekly intervals produced subacute toxicity,and one of the 2dogs that received weekly treatments,became moribund on day 19from hypocellularity of bone marrow and lymphoid tissues with necrotic tonsillitis,interdigital cellulitis and septic fever. Chronic toxicity occurred in 2/2dogs treated with weekly doses of 5mg/kg. Death from chronic toxicity occurred 74or more days after onset of treatment was related to chronic interstitial nephritis. Five of the 8dogs treated with Neocarzinostatin produced precipitating antibodies against the drug and up to 3bands of precipitation were detected by agar-gel diffusion. Evidence for immunogenic toxicity was further supported by occurrence of myocardial infarctions and anaphylactic shock in each 2/8dogs. One or 6weekly doses of 1.25mg/kg,produced no important toxicity.