Preclinical Toxicological Studies of Dichloroallyl Lawsome (ANSC 126771). Part II. Intravenous Infusion Studies.

摘要

Data are presented from four studies conducted to evaluate the preclinical toxicity of the anticancer agent dichloroallyl lawsone (NSC 126771) when administered by intravenous infusion on dosage regimes of x 1 (2-hr infusion), x 1and x 5 (1-hr infusion) in dogs,and x 5 (1-hr infusion) in monkeys. For comparison selected data are included from Part I-Injection studies in dogs. Doses administered by intravenous infusion ranged from 0.49-125mg/kg. Dogs which succumbed all died day 1after dosages of 44.7-62.5mg/kg when administered the drug by rapid injection,and 93.8-125.0mg/kg when infused over a 1-or 2-hr. period. Death occurred in monkeys after three or four doses of 31.2mg/kg or single doses of approximately equal to or more than 46.9mg/kg given by 1-hr infusion. The liver appeared to be the primary site of drug toxicity in dogs and monkeys which survived the initial dose,and elevated but readily reversible levels of serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) appeared to be the earliest and most reliable indicators of meaningful toxicity. Hematuria, bilirubinuria,and glycosuria were also observed. (Modified author abstract)